Prosthetic Valve with Aligned Inner and Outer Frames

ABSTRACT

Embodiments of the present disclosure are directed to prosthetic valves and methods of use thereof. In one implementation, an expandable prosthetic valve for implantation within a native mitral valve may be provided. The prosthetic valve may be expandable from a radially contracted state to a radially expanded state. The prosthetic valve may include an expandable outer frame and an inner frame with tissue anchors extending therefrom. The outer and inner frames may be configured and interconnected such that ventricular ends of the inner and outer frames are substantially aligned when the frames are in the radially expanded state and are not substantially aligned when the frames are in the radially contracted state.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/541,783, filed Jul. 6, 2017, now pending, which is a U.S. nationalstage entry under 35 U.S.C. §371 of International Application No.PCT/IL2016/050125, filed Feb. 3, 2016, which claims priority from U.S.Provisional Patent Application No. 62/112,343, filed Feb. 5. 2015, allof which are hereby incorporated by reference in theft entirety. Thisapplication also claims priority from U.S. Provisional PatentApplication No. 62/560 384, filed Sep. 19, 2017, which is herebyincorporated by reference in its entirety.

FIELD OF THE INVENTION

Some embodiments of the present invention relate in general to valvereplacement. More specifically, some embodiments of the presentinvention relate to prosthetic valves for replacement of a cardiacvalve.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilatation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some embodiments of the present invention, an implant is providedhaving a tubular portion, an upstream support portion and one or moreflanges. The implant is percutaneously deliverable to a native heartvalve in a compressed state, and is expandable at the native valve. Theimplant and its delivery system facilitate causing the upstream supportportion and the flanges to protrude radially outward from the tubularportion without expanding the tubular portion. Expansion of the tubularportion brings the upstream support portion and the flanges closertogether, for securing the implant at the native valve by sandwichingtissue of the native valve between the upstream support portion and theflanges.

In accordance with an embodiment of the present invention, an apparatusis provided for use with a native valve that is disposed between anatrium and a ventricle of a heart of a subject, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the tubular portion defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe: including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements to the valve-framecoupling elements is such that compression of the tubular portion fromthe expanded state toward the compressed state such that the valve-framecoupling elements pull the outer-frame coupling elements radiallyinward: (i) reduces a circumferential distance between each of theouter-frame coupling elements and its adjacent outer-frame couplingelements, and (ii) increases the amplitude of the pattern of the ring.

In an embodiment, the ring circumscribes the tubular portion.

In an embodiment, the valve-frame coupling elements are disposedcircumferentially around the longitudinal axis between the upstream endand the downstream end but not at the upstream end nor at the downstreamend.

In an embodiment, the upstream support portion includes one or morefabric pockets disposed circumferentially, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the outer frame is coupled to the valve frame only viathe fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In an embodiment, the apparatus further includes an upstream supportportion that includes a plurality of arms that extend radially from thetubular portion, and the upstream support portion has (i) aconstrained-arm state, and (ii) a released-arm state in which the armsextend radially outward from the tubular portion, each leg has atissue-engaging flange that has (i) a constrained-flange state, and (ii)a released-flange state in which the flange extends radially outwardfrom the tubular portion, and the apparatus has an intermediate state inwhich (i) the tubular portion is in its compressed state, (ii) theupstream support portion is in its released-arm state, and (iii) thelegs are in their released-flange state.

In an embodiment, the apparatus includes an implant that includes thevalve frame, the leaflets, and the outer frame, and the apparatusfurther includes a tool: including a delivery capsule dimensioned (i) tohouse and retain the implant in a compressed state of the implant inwhich (a) the tubular portion is in its compressed state, (b) theupstream support portion is in its constrained-arm state, and (c) thelegs are in their constrained-flange state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in its compressed state, and operable from outside the subject to:transition the implant from its compressed state into the intermediatestate while retaining the tubular portion in its compressed state, andsubsequently, expand the tubular portion toward its expanded state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the legs into their released-flange state, whileretaining the tubular portion in its compressed state, and (ii)subsequently, releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state.

In an embodiment, the tool is operable from outside the subject totransition the implant from its compressed state into the intermediatestate by (i) releasing the upstream support portion into itsreleased-arm state, while retaining the tubular portion in itscompressed state, and (ii) subsequently, releasing the legs into theirreleased-flange state, while retaining the tubular portion in itscompressed state.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from itscompressed state toward its expanded state moves the flangeslongitudinally away from the valve-frame coupling elements.

In an embodiment, the fixation of the outer-frame coupling elements tothe valve-frame coupling elements is such that, when the apparatus is inits intermediate state, expansion of the tubular portion from acompressed state toward an expanded state reduces the amplitude of thepattern of the ring and passes the flanges between the arms.

In an embodiment, the upstream support portion further includes acovering that covers the arms to form an annular shape in thereleased-arm state, and, when the apparatus is in its intermediatestate, expansion of the tubular portion from its compressed state towardits expanded state presses the flanges onto the covering.

In an embodiment, in the compressed state of the tubular portion, adownstream end of each leg of the tubular portion is longitudinallycloser than the valve-frame coupling elements to the downstream end, andthe flange of each leg is disposed longitudinally closer than thevalve-frame coupling elements to the upstream end.

In an embodiment, in the expanded state of the tubular portion, thedownstream end of each leg is longitudinally closer than the valve-framecoupling elements to the downstream end, and the flange of each leg isdisposed longitudinally closer than the valve-frame coupling elements tothe upstream end.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus having an implant that includes: a valve frame that includes atubular portion that circumscribes a longitudinal axis of the valveframe so as to define a lumen along the axis, the tubular portion havingan upstream end, a downstream end, a longitudinal length therebetween,and a diameter transverse to the longitudinal axis; a valve member,coupled to the tubular portion, disposed within the lumen, and arrangedto provide unidirectional upstream-to-downstream flow of blood throughthe lumen; an upstream support portion, coupled to the tubular portion;and an outer frame, coupled to the tubular portion, and including atissue-engaging flange, and: the implant has a first state and a secondstate, in both the first state and the second state, (i) the upstreamsupport portion extends radially outward from the tubular portion, and(ii) the tissue-engaging flange extends radially outward from thetubular portion, and the tubular portion, the upstream support portion,and the outer frame are arranged such that transitioning of the implantfrom the first state toward the second state: increases the diameter ofthe tubular portion by a diameter-increase amount, decreases the lengthof the tubular portion by a length-decrease amount, and moves the flangea longitudinal distance toward or toward-and-beyond the upstream supportportion, the distance being greater than the length-decrease amount.

In an embodiment of the present invention, the tubular portion, theupstream support portion, and the outer frame may be arranged such thatthe longitudinal distance is more than 20 percent greater than thelength-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 30 percent greater than the length-decrease amount.

In an embodiment, the tubular portion, the upstream support portion, andthe outer frame may be arranged such that the longitudinal distance ismore than 40 percent greater than the length-decrease amount.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis; a plurality of prosthetic leaflets, coupled to the frame, disposedwithin the lumen, and arranged to provide unidirectional flow of bloodfrom an upstream end of the lumen to a downstream end of the lumen; anouter frame, including: a ring defined by a pattern of alternating peaksand troughs: the peaks being longitudinally closer than the troughs tothe upstream end, the peaks being fixed to respective sites of thetubular portion at respective coupling points disposed circumferentiallyaround the longitudinal axis, and the pattern of the ring having anamplitude longitudinally between the peaks and the troughs; and aplurality of legs, each of the legs coupled to the ring at a respectivetrough, and: the tubular portion has (i) a compressed state in which thetubular portion has a compressed diameter, and (ii) an expanded state inwhich the tubular portion has an expanded diameter that is greater thanthe compressed diameter, and the fixation of the peaks to the respectivesites of the tubular portion is such that compression of the tubularportion from the expanded state toward the compressed state such thatthe respective sites of the tubular portion pull the peaks radiallyinward via radially-inward tension on the coupling points: (i) reduces acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) increases the amplitude of thepattern of the ring.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve that is disposed between an atrium and aventricle of a heart of a subject is provided, the apparatus including:a valve frame, including a tubular portion that circumscribes alongitudinal axis of the valve frame so as to define a lumen along theaxis, the valve frame defining a plurality of valve-frame couplingelements disposed circumferentially around the longitudinal axis; aplurality of prosthetic leaflets, coupled to the frame, disposed withinthe lumen, and arranged to provide unidirectional flow of blood from anupstream end of the lumen to a downstream end of the lumen; an outerframe: including a ring defined by a pattern of alternating peaks andtroughs, the peaks being longitudinally closer to the upstream end thanto the downstream end, and the troughs being longitudinally closer tothe downstream end than to the upstream end, and the pattern of the ringhaving an amplitude longitudinally between the peaks and the troughs,including a plurality of legs, each of the legs coupled to the ring at arespective trough, and shaped to define a plurality of outer-framecoupling elements, each of the outer-frame coupling elements (i) coupledto the ring at a respective peak, and (ii) fixed with respect to arespective valve-frame coupling element, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the outer-frame coupling elements with respect to thevalve-frame coupling elements is such that compression of the tubularportion from the expanded state toward the compressed state (i) pullsthe outer-frame coupling elements radially inward via radially-inwardpulling of the valve-frame coupling elements on the outer-frame couplingelements, (ii) reduces a circumferential distance between each of theouter-frame coupling elements and its adjacent outer-frame couplingelements, and (iii) increases the amplitude of the pattern of the ring,without increasing a radial gap between the valve frame and the ring bymore than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

There is further provided, in accordance with an embodiment of thepresent invention, an apparatus for use with a native valve that isdisposed between an atrium and a ventricle of a heart of a subject isprovided, the apparatus including: a valve frame, including a tubularportion that circumscribes a longitudinal axis of the valve frame so asto define a lumen along the axis; a plurality of prosthetic leaflets,coupled to the frame, disposed within the lumen, and arranged to provideunidirectional flow of blood from an upstream end of the lumen to adownstream end of the lumen; an outer frame, including: a ring definedby a pattern of alternating peaks and troughs: the peaks beinglongitudinally closer than the troughs to the upstream end, the peaksbeing fixed to respective sites of the tubular portion at respectivecoupling points disposed circumferentially around the longitudinal axis,and the pattern of the ring having an amplitude longitudinally betweenthe peaks and the troughs; and a plurality of legs, each of the legscoupled to the ring at a respective trough, and: the tubular portion has(i) a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and thefixation of the peaks to the respective sites of the tubular portion issuch that compression of the tubular portion from the expanded statetoward the compressed state (i) pulls the peaks radially inward viaradially-inward pulling of the respective sites of the tubular portionon the peaks, (ii) reduces a circumferential distance between each ofthe coupling points and its adjacent coupling points, and (iii)increases the amplitude of the pattern of the ring, without increasing aradial gap between the valve frame and the ring by more than 1.5 mm.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end, a downstream end, and defining aplurality of valve-frame coupling elements disposed circumferentiallyaround the longitudinal axis between the upstream end and the downstreamend but not at the upstream end nor at the downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frame:including a ring defined by a pattern of alternating peaks and troughs,the peaks being longitudinally closer to the upstream end than to thedownstream end, and the troughs being longitudinally closer to thedownstream end than to the upstream end, including a plurality of legs,each of the legs coupled to the ring at a respective trough, and shapedto define a plurality of outer-frame coupling elements, each of theouter-frame coupling elements (i) coupled to the ring at a respectivepeak, and (ii) fixed with respect to a respective valve-frame couplingelement at a respective coupling point, and: the tubular portion has (i)a compressed state in which the tubular portion has a compresseddiameter, and (ii) an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, andexpansion of the tubular portion from the compressed state toward theexpanded state (i) increases a circumferential distance between each ofthe outer-frame coupling elements and its adjacent outer-frame couplingelements, and (ii) moves the plurality of legs in a longitudinallyupstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the outer-frame coupling elements to the respectivevalve-frame coupling elements.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a valveframe, including a tubular portion that circumscribes a longitudinalaxis of the valve frame so as to define a lumen along the axis, thetubular portion having an upstream end and a downstream end; a pluralityof prosthetic leaflets, disposed within the lumen, and arranged toprovide unidirectional flow of blood through the lumen; an outer frame,including: a ring defined by a pattern of alternating peaks and troughs:the peaks being longitudinally closer than the troughs to the upstreamend, the peaks being fixed to respective sites of the tubular portion atrespective coupling points disposed circumferentially around thelongitudinal axis between the upstream end and the downstream end butnot at the upstream end nor the downstream end; and a plurality of legs,each of the legs coupled to the ring at a respective trough, and: thetubular portion has (i) a compressed state in which the tubular portionhas a compressed diameter, and (ii) an expanded state in which thetubular portion has an expanded diameter that is greater than thecompressed diameter, and expansion of the tubular portion from thecompressed state toward the expanded state (i) increases acircumferential distance between each of the coupling points and itsadjacent coupling points, and (ii) moves the plurality of legs in alongitudinally upstream direction with respect to the tubular portion.

In an embodiment, the outer frame may be coupled to the valve frame onlyvia the fixation of the peaks to the respective sites of the tubularportion at the respective coupling points.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including: a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: a valve frame, including: a tubular portion having anupstream end and a downstream end, and shaped to define a lumentherebetween, and an upstream support portion, extending from theupstream end of the tubular portion; and at least one leg, coupled tothe valve frame at a coupling point, and having a tissue-engagingflange; and a valve member disposed within the lumen, and configured tofacilitate one-way liquid flow through the lumen from the upstream endof the tubular portion to the downstream end of the tubular portion, andthe frame assembly: has a compressed state, for percutaneous delivery tothe heart, in which the tubular portion has a compressed diameter, isbiased to assume an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and isconfigured such that increasing the diameter of the tubular portiontoward the expanded diameter causes longitudinal movement: of theupstream support portion toward the coupling point, and of thetissue-engaging flange away from the coupling point.

In an embodiment: the apparatus includes an implant that includes theframe assembly and the valve member, and the apparatus further includesa tool: including a delivery capsule dimensioned (i) to house and retainthe implant in the compressed state, and (ii) to be advancedpercutaneously to the heart of the subject while the implant is housedand in the compressed state, and operable from outside the subject tofacilitate an increase of the diameter of the tubular portion from thecompressed diameter toward the expanded diameter such that the increaseof the diameter actuates longitudinal movement: of the upstream supportportion toward the coupling point, and of the tissue-engaging flangeaway from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes longitudinal movement of theupstream end of the tubular portion toward the coupling point.

In an embodiment, the coupling point is disposed closer to thedownstream end of the frame assembly than are either the tissue-engagingflange or the upstream support portion.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis.

In an embodiment, the expanded state of the frame assembly may be afully-expanded state of the frame assembly, the leg is expandable intoan expanded state of the leg, independently of increasing the diameterof the tubular portion, and in the expanded state of the leg, the legextends away from the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, the legextends away from the central longitudinal axis, and in the compressedstate of the frame assembly, the leg is generally parallel with thecentral longitudinal axis.

In an embodiment, the frame assembly may be configured such that thelongitudinal movement of the tissue-engaging flange away from thecoupling point is a translational movement of the tissue-engaging flangethat does not include rotation of the tissue-engaging flange.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the tissue-engaging flange away from the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state causes 1-20 mm of longitudinalmovement of the upstream support portion toward the coupling point.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state reduces a distance between theupstream support portion and the tissue-engaging flange by 5-30 mm.

In an embodiment, the frame assembly may be configured such thatincreasing the diameter of the tubular portion by expanding the frameassembly toward the expanded state moves the tissue-engaging flangelongitudinally past the upstream support portion.

In an embodiment, the tubular portion may be defined by a plurality ofcells of the valve frame, and increasing the diameter of the tubularportion by expanding the frame assembly toward the expanded state:includes (i) increasing a width, orthogonal to the longitudinal axis ofthe frame assembly, of each cell, and (ii) reducing a height, parallelwith the longitudinal axis of the frame assembly, of each cell, andcauses longitudinal movement of the upstream support portion toward thecoupling point by reducing a height, parallel with the longitudinal axisof the frame assembly, of the tubular portion, by reducing the height ofeach cell.

In an embodiment, the leg is disposed on an outside of the tubularportion.

In an embodiment, the at least one leg includes a plurality of legs, thecoupling point includes a plurality of coupling points, and the frameassembly includes a leg frame that circumscribes the tubular portion,includes the plurality of legs, and is coupled to the valve frame at theplurality of coupling points, such that the plurality of legs isdistributed circumferentially around the tubular portion.

In an embodiment, the plurality of coupling points is disposedcircumferentially around the frame assembly on a transverse plane thatis orthogonal to the longitudinal axis of the frame assembly.

In an embodiment, the plurality of legs may be coupled to the valveframe via a plurality of struts, each strut having a first end that iscoupled to a leg of the plurality of legs, and a second end that iscoupled to a coupling point of the plurality of coupling points, in thecompressed state of the frame assembly, being disposed at a first anglein which the first end is disposed closer to the downstream end of theframe assembly than is the second end, and being deflectable withrespect to the coupling point of the plurality of coupling points, suchthat increasing the diameter of the tubular portion by expanding theframe assembly toward the expanded state causes the strut to deflect toa second angle in which the first end is disposed further from thedownstream end of the frame assembly than is the first end in thecompressed state of the frame assembly.

In an embodiment, the leg frame may be structured such that each leg ofthe plurality of legs is coupled to two struts of the plurality ofstruts, and two struts of the plurality of struts are coupled to eachcoupling point of the plurality of coupling points.

In an embodiment, the leg may be coupled to the valve frame via a strut,the strut having a first end that is coupled to the leg, and a secondend that is coupled to the coupling point, in the compressed state ofthe frame assembly, being disposed at a first angle in which the firstend is disposed closer to the downstream end of the frame assembly thanis the second end, and being deflectable with respect to the couplingpoint, such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causes the strutto deflect to a second angle in which the first end is disposed furtherfrom the downstream end of the frame assembly than is the first end inthe compressed state of the frame assembly.

In an embodiment, the at least one leg includes at least a first leg anda second leg.

In an embodiment, the first leg and the second leg are both coupled tothe valve frame at the coupling point.

In an embodiment, the first leg may be coupled to the coupling point viaa respective first strut, and the second leg is coupled to the couplingpoint via a respective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly: the coupling point is disposed,circumferentially with respect to the tubular portion, between the firststrut and the second strut, the first strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the first leg, and the second strut is disposed,circumferentially with respect to the tubular portion, between thecoupling point and the second leg.

In an embodiment, the coupling point includes at least a first couplingpoint and a second coupling point.

In an embodiment, the leg is coupled to the valve frame at the firstcoupling point and at the second coupling point.

In an embodiment, the leg may be coupled to the first coupling point viaa respective first strut, and to the second coupling point via arespective second strut.

In an embodiment, the first and second legs, the first and secondstruts, and the coupling point are arranged such that, in the expandedstate of the frame assembly: the leg is disposed, circumferentially withrespect to the tubular portion, between the first strut and the secondstrut, the first strut is disposed, circumferentially with respect tothe tubular portion, between the leg and the first coupling point, andthe second strut is disposed, circumferentially with respect to thetubular portion, between the leg and the second coupling point.

In an embodiment, in the expanded state of the frame assembly, theupstream support portion extends radially outward from the tubularportion.

In an embodiment, the expanded state of the frame assembly is afully-expanded state of the frame assembly, the upstream support portionis expandable into an expanded state of the upstream support portion,independently of increasing the diameter of the tubular portion, and inthe expanded state of the upstream support portion, the upstream supportportion extends radially outward from the tubular portion.

In an embodiment, in the compressed state of the frame assembly, theupstream support portion is generally tubular, collinear with thetubular portion, and disposed around the central longitudinal axis.

In an embodiment, in the expanded state of the frame assembly, an innerregion of the upstream support portion extends radially outward from thetubular portion at a first angle with respect to the tubular portion,and an outer region of the upstream support portion extends, from theinner region of the upstream support portion, further radially outwardfrom the tubular portion at a second angle with respect to the tubularportion, the second angle being smaller than the first angle.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: a valve frame, including: a tubular portion having anupstream end and a downstream end, and shaped to define a lumentherebetween, and an upstream support portion, extending from theupstream end of the tubular portion; and at least one leg, coupled tothe valve frame at a coupling point, and having a tissue-engagingflange; and a valve member disposed within the lumen, and configured tofacilitate one-way liquid flow through the lumen from the upstream endof the tubular portion to the downstream end of the tubular portion, andthe frame assembly: has a compressed state, for percutaneous delivery tothe heart, in which the tubular portion has a compressed diameter, isbiased to assume an expanded state in which the tubular portion has anexpanded diameter that is greater than the compressed diameter, and isconfigured such that reducing the diameter of the tubular portion towardthe compressed diameter causes longitudinal movement of the upstreamsupport portion away from the coupling point, and of the tissue-engagingflange toward the coupling point.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, including:a valve frame, including: a tubular portion having an upstream end and adownstream end, and shaped to define a lumen therebetween, and anupstream support portion, extending from the upstream end of the tubularportion; and at least one leg, coupled to the valve frame at a couplingpoint, and having a tissue-engaging flange; and a valve member disposedwithin the lumen, and configured to facilitate one-way liquid flowthrough the lumen from the upstream end of the tubular portion to thedownstream end of the tubular portion, and the frame assembly: has acompressed state, for percutaneous delivery to the heart, isintracorporeally expandable into an expanded state in which a diameterof the tubular portion is greater than in the compressed state, and isconfigured such that increasing the diameter of the tubular portion byexpanding the frame assembly toward the expanded state causeslongitudinal movement of the tissue-engaging flange away from thecoupling point.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve of a heart of a subject is provided, theapparatus including a frame assembly, having an upstream end and adownstream end, and a central longitudinal axis therebetween, andincluding: an inner frame including an inner-frame tubular portion thatcircumscribes the central longitudinal axis, has an upstream end and adownstream end, and defines a channel therebetween, the inner framedefining a plurality of inner-frame couplings disposed circumferentiallyat a longitudinal location of the inner frame, an outer frame includingan outer-frame tubular portion that coaxially circumscribes at least aportion of the inner-frame tubular portion, the outer frame defining aplurality of outer-frame couplings disposed circumferentially at alongitudinal location of the outer frame, and a plurality of connectors,each connector connecting a respective inner-frame coupling to arespective outer-frame coupling; a liner, disposed over at least part ofthe inner-frame tubular portion; and a plurality of prosthetic leaflets,coupled to the inner-frame tubular portion and disposed within thechannel, and: the frame assembly: (i) is compressible by aradially-compressive force into a compressed state in which the innerframe is in a compressed state thereof and the outer frame is in acompressed state thereof, (ii) is configured, upon removal of theradially-compressive force, to automatically expand into an expandedstate thereof in which the inner frame is in an expanded state thereofand the outer frame is in an expanded state thereof, in the expandedstate of the frame assembly, the prosthetic leaflets are configured tofacilitate one-way fluid flow, in a downstream direction, through thechannel, and the connection of the inner-frame couplings to therespective outer-frame couplings is such that expansion of the frameassembly from the compressed state to the expanded state causes theinner-frame tubular portion to slide longitudinally in a downstreamdirection with respect to the outer-frame tubular portion.

In accordance with an embodiment of the present invention, an apparatusfor use with a native valve disposed between an atrium and a ventricleof a heart of a subject is provided, the apparatus including: a tubularportion, having an upstream portion that includes an upstream end, and adownstream portion that includes a downstream end, and shaped to definea lumen between the upstream portion and the downstream portion; aplurality of prosthetic leaflets, disposed within the lumen, andarranged to provide unidirectional flow of blood from the upstreamportion to the downstream portion; an annular upstream support portion:having an inner portion that extends radially outward from the upstreamportion, and including one or more fabric pockets disposedcircumferentially around the inner portion, each pocket of the one ormore pockets having an opening that faces a downstream direction.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the inner portion of the upstream supportportion, the covering is closely-fitted between the radially-inner partsof the arms, and at the outer portion of the upstream support portion,the pockets are formed by the covering being loosely-fitted between theradially-outer parts of the arms.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, the radially-outer part being more flexiblethan the radially-inner part.

In an embodiment, the upstream support portion includes (i) a pluralityof arms that extend radially outward from the tubular portion, and (ii)a covering, disposed over the plurality of arms, each arm has (i) aradially-inner part at the inner portion of the upstream supportportion, and (ii) a radially-outer part at the outer portion of theupstream support portion, at the outer portion of the upstream supportportion, the pockets are formed by each arm curving to form a hookshape.

In an embodiment, each pocket may be shaped and arranged to billow inresponse to perivalvular flow of blood in an upstream direction.

In an embodiment, the apparatus may be configured to be transluminallydelivered to the heart and implanted at the native valve by expansion ofthe apparatus, such that the upstream support portion is disposed in theatrium and the tubular portion extends from the upstream support portioninto the ventricle, and each pocket is shaped and arranged such thatperivalvular flow of blood in an upstream direction presses the pocketagainst tissue of the atrium.

In accordance with an embodiment of the present invention, an apparatusis provided including a plurality of prosthetic valve leaflets; and aframe assembly, including: a tubular portion defined by a repeatingpattern of cells, the tubular portion extending circumferentially arounda longitudinal axis so as to define a longitudinal lumen, the prostheticvalve leaflets coupled to the inner frame and disposed within the lumen;an outer frame, including a plurality of legs, distributedcircumferentially around the tubular portion, each leg having atissue-engaging flange; an upstream support portion that includes aplurality of arms that extend radially outward from the tubular portion;and a plurality of appendages, each having a first end that defines acoupling element via which the tubular portion is coupled to the outerframe, and a second end; and the frame assembly defines a plurality ofhubs, distributed circumferentially around the longitudinal axis on aplane that is transverse to the longitudinal axis, each hub defined byconvergence and connection of, (i) two adjacent cells of the tubularportion, (ii) an arm of the plurality of arms, and (iii) an appendage ofthe plurality of appendages.

In an embodiment, each hub has six radiating spokes, two of the sixspokes being part of a first cell of the two adjacent cells, two of thesix spokes being part of a second cell of the two adjacent cells, one ofthe six spokes being the arm, and one of the six spokes being the secondend of the appendage.

In an embodiment, the appendages are in-plane with the tubular portion.

In an embodiment, the appendages are in-plane with the outer frame.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant: including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that a tissue-engaging flange of the leg is disposed downstream ofthe valve, and thereafter causing the flange to protrude radiallyoutward from the axis; subsequently, while an upstream support portionof the valve frame is disposed upstream of the valve, causing theupstream support portion to protrude radially outward from the axis,such that tissue of the valve is disposed between the upstream supportportion and the flange; and subsequently, sandwiching the tissue betweenthe upstream support portion and the flange by reducing a distancebetween the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding percutaneously advancing to heart, an implant: including avalve frame, a valve member disposed within a lumen defined by the valveframe, and at least one leg, coupled to the valve frame at a couplingpoint, and having an upstream end, a downstream end, and a centrallongitudinal axis therebetween; positioning the implant within the heartsuch that an upstream support portion of the valve frame is disposedupstream of the valve, and thereafter causing the upstream supportportion to protrude radially outward from the axis; subsequently, whilea tissue-engaging flange of the leg is disposed downstream of the valve,causing the tissue-engaging flange to protrude radially outward from theaxis, such that tissue of the valve is disposed between the upstreamsupport portion and the flange; and subsequently, sandwiching the tissuebetween the upstream support portion and the flange by reducing adistance between the upstream support portion and the flange by causinglongitudinal movement (i) of the upstream support portion toward thecoupling point, and (ii) of the tissue-engaging flange away from thecoupling point.

In an embodiment, causing the longitudinal movement (i) of the upstreamsupport portion toward the coupling point, and (ii) of thetissue-engaging flange away from the coupling point, includes causingthe longitudinal movement by increasing a diameter of the lumen.

In accordance with an embodiment of the present invention, a method foruse with a native valve of a heart of a subject is provided, the methodincluding: percutaneously advancing an implant to the heart, the implanthaving an upstream end, a downstream end, and a central longitudinalaxis therebetween, and including a tubular portion, an upstream supportportion, and a plurality of tissue-engaging flanges; positioning theimplant within the heart such that the upstream support portion isdisposed upstream of the valve, positioning the implant within the heartsuch that the tissue-engaging flanges are disposed downstream of thevalve, without increasing a diameter of the tubular portion: causing theupstream support portion to extend radially outward from the axis so asto have a first support-portion span, and causing the flanges to extendradially outward from the axis so as to have a first flange span; andsubsequently, causing the upstream support portion and the flanges movetoward each other by at least 5 mm by increasing a diameter of thetubular portion such that: the upstream support portion extends radiallyoutward so as to have a second support-portion span, the firstsupport-portion span being at least 40 percent as great as the secondsupport-portion span, and the flanges extend radially outward so as tohave a second flange span, the first flange span being at least 30percent as great as the second flange span.

There is further provided, in accordance with an application of thepresent invention, a method for use with a native valve of a heart of asubject, the method including: percutaneously advancing an implant tothe heart, the implant: having an upstream end, a downstream end, and acentral longitudinal axis therebetween, and including a tubular portion,an upstream support portion, and a plurality of tissue-engaging flanges;positioning the implant within the heart such that the upstream supportportion is disposed upstream of the valve, positioning the implantwithin the heart such that the tissue-engaging flanges are disposeddownstream of the valve, without increasing a diameter of the tubularportion: causing the upstream support portion to extend radially outwardfrom the axis, and causing the flanges to extend radially outward fromthe axis so as to have a first flange span; and subsequently, byincreasing a diameter of the tubular portion: causing the upstreamsupport portion and the flanges move toward each other by at least 5 mm,causing the upstream support portion to move further radially outwardfrom the axis, and causing each flange of the plurality of flanges totranslate radially outward so as to have a second flange span that isgreater than the first flange span.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B and 2A-E are schematic illustrations of an implant for usewith a native valve of a heart of a subject, in accordance with someapplications of the invention;

FIGS. 3A-C are schematic illustrations that show structural changes in aframe assembly during transitioning of the assembly between itscompressed and expanded states, in accordance with some applications ofthe invention;

FIGS. 4A-F are schematic illustrations of implantation of the implant atthe native valve, in accordance with some applications of the invention;

FIG. 5 is a schematic illustration of a step in the implantation of theimplant, in accordance with some applications of the invention;

FIG. 6 is a schematic illustration of the implant, in accordance withsome applications of the invention;

FIGS. 7A-B and 8A-B are schematic illustrations of frame assemblies ofrespective implants, in accordance with some applications of theinvention; and

FIGS. 9A-C are schematic illustrations of an implant comprising a frameassembly, in accordance with some applications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-B and 2A-E, which are schematicillustrations of an implant 20 (alternatively, “prosthetic valve 20”)for use with a native valve of a heart of a subject, in accordance withsome embodiments of the invention. Prosthetic valve 20 comprises a frameassembly 22 that has an upstream end 24 (alternatively, “atrial end24”), a downstream end 26 (alternatively, “ventricular end 26”), and acentral longitudinal axis ax1 therebetween. The term “atrial end” mayrefer to an end of a given feature configured to be situated closest toan atrium of the heart when prosthetic valve 20 is implanted therein.For example, in FIGS. 1A, 1B, 2A-E, and 4A-F, the atrial end ofprosthetic valve 20 may be the top end of prosthetic valve 20.Similarly, the term “ventricular end” may refer to an end of a givenfeature configured to be situated closest to a ventricle of the heartwhen prosthetic valve 20 is implanted therein. For example, in FIGS. 1A,1B, 2A-E, and 4A-F, the ventricular end of prosthetic valve 20 may bethe bottom end of prosthetic valve 20. Frame assembly 22 comprises avalve frame 30 (alternatively “inner frame 30”) that comprises a tubularportion 32 (alternatively, “inner frame tubular portion 32”) that has anatrial end 34 and a ventricular end 36, and is shaped to define a lumen38 through the inner frame tubular portion 32 from the atrial end to theventricular end. As illustrated in FIGS. 1A and 1B, inner frame tubularportion 32 may also include one or more projections 28, which extendfrom ventricular end 36 of inner frame tubular portion 32. Inner frametubular portion 32 circumscribes axis ax1, and thereby defines lumen 38along the axis. Inner frame 30 further comprises an atrial supportportion 40, extending from atrial end 34 of inner frame tubular portion32. Frame assembly 22 further comprises at least one leg 50(alternatively, “ventricular anchor support 50”), coupled to inner frame30 at (e.g., via) a coupling point 52, and having a tissue-engagingflange 54 (alternatively, “outer frame tissue anchor 54”).

In some embodiments, and as described hereinbelow, ventricular anchorsupport 50 is part of an outer frame 60, and frames 30 and 60 definerespective coupling elements 31 and 61, which are fixed with respect toeach other at coupling points 52. As illustrated in FIG. 1A, inner frame30 may be positioned at least partially within outer frame 60. In someembodiments, frames 30 and 60 are coupled to each other only at couplingpoints 52 (e.g., only via the fixation of coupling elements 31 and 61with respect to each other).

Prosthetic valve 20 further comprises a valve member 58 (e.g., one ormore prosthetic leaflets) disposed within lumen 38, and configured tofacilitate one-way liquid flow through the lumen from atrial end 34 toventricular end 36 (e.g., thereby defining the orientation of the atrialand ventricular ends of inner frame tubular portion 32). FIG. 1A showsprosthetic valve 20 in a fully-expanded state (alternatively, “radiallyexpanded state”), in which frame assembly 22 is in a radially expandedstate. FIG. 1B shows an exploded view of frame assembly 22 in itsradially expanded state. FIGS. 2A-E show respective states of prostheticvalve 20, which will be discussed in more detail hereinbelow withrespect to the implantation of the prosthetic valve and the anatomy inwhich the prosthetic valve is implanted. FIG. 2A shows prosthetic valve20 in a compressed state (alternatively, “radially contracted state”),in which frame assembly 22 is in a radially contracted state forpercutaneous delivery of the prosthetic valve to the heart of thesubject. In some embodiments, in the radially contracted state,ventricular anchor support 50 (including outer frame tissue anchor 54thereof) is in a constrained-anchor state in which the outer frametissue anchor is generally parallel with axis ax1. Further, in theradially contracted state, atrial support portion 40 is generallytubular, collinear with inner frame tubular portion 32 (e.g., extendingcollinearly from the inner frame tubular portion), and disposed aroundaxis ax1.

FIG. 2B shows a state of prosthetic valve 20 in which outer frame tissueanchor 54 of each ventricular anchor support 50 extends radially awayfrom axis ax1 (e.g., radially away from inner frame tubular portion 32).FIG. 2C shows a state of prosthetic valve 20 in which atrial supportportion 40 extends radially away from axis ax1 (and thereby radiallyaway from inner frame tubular portion 32). FIG. 2D shows a state ofprosthetic valve 20 in which both outer frame tissue anchor 54 andatrial support portion 40 extend away from axis ax1. In the radiallyexpanded state (FIGS. 1A-B) both atrial support portion 40 and outerframe tissue anchor 54 extend radially away from axis ax1. In someembodiments, frame assembly 22 is biased (e.g., shape-set) to assume itsradially expanded state, which is shown in FIG. 2E. Transitioning ofprosthetic valve 20 between the respective states may be controlled bydelivery apparatus, such as by constraining the prosthetic valve in aradially contracted state within a delivery tube and/or against acontrol rod, and selectively releasing portions of the prosthetic valveto allow them to expand.

In the radially contracted state of frame assembly 22, inner frametubular portion 32 has a diameter d1, and in the radially expandedstate, the inner frame tubular portion has a diameter d2 that is greaterthat diameter d1. For some embodiments, diameter d1 is 4-15 mm, (e.g.,5-11 mm) and diameter d2 is 20-50 mm, (e.g., 23-33 mm). Frame assembly22 is configured such that increasing the diameter of inner frametubular portion 32 (e.g., from d1 to d2) causes longitudinal movement ofouter frame tissue anchor 54 away from coupling point 52. In the sameway, reducing the diameter of inner frame tubular portion 32 (e.g., fromd2 to d1) causes longitudinal movement of outer frame tissue anchor 54toward coupling point 52. It is to be noted that the term “longitudinalmovement” (including the specification and the claims) means movementparallel with central longitudinal axis ax1. Therefore longitudinalmovement of outer frame tissue anchor 54 away from coupling point 52means increasing a distance, measured parallel with longitudinal axisax1, between outer frame tissue anchor 54 and coupling point 52. Anexample of such a configuration is described in more detail with respectto FIG. 3A.

Thus, expansion of inner frame tubular portion 32 from its radiallycontracted state toward its radially expanded state (i) increases acircumferential distance between each of coupling points 52 and itsadjacent coupling points (e.g., between each of outer-frame couplingelements 61 and its adjacent outer-frame coupling elements) (e.g., fromd8 to d9), and (ii) moves ventricular anchor support 50 in alongitudinally atrial direction with respect to the inner frame tubularportion. The term “atrial direction” may refer to a direction extendingupstream from prosthetic valve 20, towards an atrium of the heart. Forexample, in FIGS. 4A-4F, an “atrial direction” may refer to a directionextending upwards from prosthetic valve 20 towards atrium 6. Similarly,the term “ventricular direction” may refer to a direction extendingdownstream from prosthetic valve 20, towards a ventricle of the heart.For example, in FIGS. 4A-4F, a “ventricular direction” may refer to adirection extending downwards from prosthetic valve 20 towards ventricle8.

In some embodiments, frame assembly 22 is configured such thatincreasing the diameter of inner frame tubular portion 32 also causeslongitudinal movement of atrial support portion 40 toward coupling point52, e.g., as described in more detail with respect to FIGS. 3B-C. Insome embodiments, frame assembly 22 is configured such that increasingthe diameter of inner frame tubular portion 32 also causes longitudinalmovement of atrial end 34 of inner frame tubular portion 32 towardcoupling point 52. In the same way, reducing the diameter of inner frametubular portion 32 causes longitudinal movement of atrial end 34 awayfrom coupling point 52.

For some embodiments, atrial support portion 40 comprises a plurality ofinner frame tissue anchors 46 that each extends radially outward frominner frame tubular portion 32 (e.g., from atrial end 34 of the innerframe tubular portion). Inner frame tissue anchors 46 are flexible. Forsome such embodiments, inner frame tissue anchors 46 are coupled toinner frame tubular portion 32 such that each inner frame tissue anchormay deflect independently of adjacent inner frame tissue anchors 46during implantation (e.g., due to anatomical topography).

For some embodiments, atrial support portion 40 comprises a plurality ofbarbs 48 that extend out of a ventricular surface of the atrial supportportion. For example, each inner frame tissue anchor 46 may comprise oneor more of barbs 48. Barbs 48 press into tissue on an atrial side of thenative valve (e.g., into the valve annulus), thereby inhibiting movementof prosthetic valve 20 in a ventricular direction (in addition toinhibition of movement in a ventricular direction provided by thegeometry of atrial support portion 40).

One or more surfaces of frame assembly 22 are covered with a covering23, which comprises a flexible sheet, such as a fabric, e.g., comprisingpolyester. In some embodiments, covering 23 covers at least part ofinner frame tubular portion 32, lining an inner surface of the innerframe tubular portion, and thereby defining lumen 38.

Further, atrial support portion 40 is covered with covering 23, e.g.,extending between inner frame tissue anchors 46 to form an annularshape. It is hypothesized that this reduces a likelihood of paravalvularleakage. For such embodiments, excess covering 23 may be providedbetween inner frame tissue anchors 46 of atrial support portion 40, soas to facilitate their independent movement. Although FIG. 1A showscovering 23 covering an atrial side of atrial support portion 40, thecovering additionally (or alternatively) covers the ventricular side ofthe atrial support portion. For example, covering 23 may extend over thetips of inner frame tissue anchors 46 and down the outside of the innerframe tissue anchors, or a separate piece of covering may be provided onthe ventricular side of the atrial support portion.

Alternatively, each inner frame tissue anchor 46 may be individuallycovered in a sleeve of covering 23, thereby facilitating independentmovement of the inner frame tissue anchors.

For some embodiments, at least a portion of ventricular anchor support50 (e.g., outer frame tissue anchors 54 thereof) is covered withcovering 23.

In some embodiments, frame assembly 22 comprises a plurality ofventricular anchor supports 50 (e.g., two or more ventricular anchorsupports, e.g., 2-16 ventricular anchor supports, such as 4-12ventricular anchor supports, such as 6-12 ventricular anchor supports),arranged circumferentially around inner frame 30 (e.g., around theoutside of inner frame tubular portion 32). In some embodiments, frameassembly 22 comprises a plurality of coupling points 52 at which theventricular anchor supports are coupled to inner frame 30.

As described in more detail hereinbelow (e.g., with reference to FIG.3A), each ventricular anchor support 50 may be coupled to a couplingpoint 52 via a strut 70. For some embodiments, each ventricular anchorsupport 50 is coupled to a plurality of (e.g., two) coupling points 52via a respective plurality of (e.g., two) struts 70. For some suchembodiments, frame assembly 22 is arranged such that, in the radiallyexpanded state of the frame assembly, ventricular anchor support 50 isdisposed, circumferentially with respect to inner frame tubular portion32, between two struts, and each of the two struts are disposed,circumferentially with respect to the inner frame tubular portion,between the ventricular anchor support and a respective coupling point52.

For some embodiments, a plurality of (e.g., two) ventricular anchorsupports 50 are coupled to each coupling point 52 via a respectiveplurality of (e.g., two) struts 70. For some such embodiments, frameassembly 22 is arranged such that, in the radially expanded state of theframe assembly, coupling point 52 is disposed, circumferentially withrespect to inner frame tubular portion 32, between two struts 70, andeach of the two struts are disposed, circumferentially with respect tothe inner frame tubular portion, between the coupling point and arespective ventricular anchor support 50.

For some embodiments, frame assembly 22 comprises an outer frame 60 thatcircumscribes inner frame tubular portion 32, comprises (or defines) theplurality of ventricular anchoring supports 50 and the plurality ofstruts 70, and is coupled to inner frame 30 at the plurality of couplingpoints 52, such that the plurality of ventricular anchoring supports aredistributed circumferentially around the inner frame tubular portion.For such embodiments, outer frame 60 comprises a ring 66 that is definedby a pattern of alternating peaks 64 and troughs 62, and thatcircumscribes inner frame tubular portion 32. For example, the ring maycomprise struts 70, extending between the peaks and troughs. Peaks 64are longitudinally closer to atrial end 34 of inner frame tubularportion 32 than to ventricular end 36, and troughs 62 are longitudinallycloser to the ventricular end than to the atrial end. (It is to be notedthat throughout this patent application, including the specification andthe claims, the term “longitudinally” means with respect to longitudinalaxis ax1. For example, “longitudinally closer” means closer along axisax1 (whether positioned on axis ax1 or lateral to axis ax1), and“longitudinal movement” means a change in position along axis ax1 (whichmay be in additional to movement toward or away from axis ax1).Therefore, peaks 64 are closer than troughs 62 to atrial end 34, andtroughs 62 are closer than peaks 64 to ventricular end 36. Asillustrated in FIG. 1B, outer frame 60 may include multiple rings 66(e.g. two rings 66) which are connected by ventricular anchoringsupports 50. Rings 66 and ventricular anchor supports 50 may form anannular outer frame tubular portion 65. Annular outer frame tubularportion 65 may have an atrial end 67 and a ventricular end 69, and maycircumscribe axis ax1. As also illustrated in FIG. 1B, outer frametissue anchors 54 may extend from annular outer frame tubular portion65. For embodiments in which frame 60 comprises ring 66, eachventricular anchor support 50 is coupled to the ring (or defined byframe 60) at a respective trough 62.

In the embodiment shown, the peaks and troughs are defined by ring 66having a generally zig-zag shape. However, the scope of the inventionincludes ring 66 having another shape that defines peaks and troughs,such as a serpentine or sinusoid shape.

For embodiments in which frame assembly 22 has a plurality of couplingpoints 52, the coupling points (and therefore coupling elements 31 and61) are disposed circumferentially around the frame assembly (e.g.,around axis ax1), in some embodiments on a transverse plane that isorthogonal to axis ax1. This transverse plane is illustrated by theposition of section A-A in FIG. 2B. Alternatively, coupling points 52may be disposed at different longitudinal heights of frame assembly 22,e.g., such that different outer frame tissue anchors 54 are positionedand/or moved differently to others. In some embodiments, coupling points52 (and therefore coupling elements 31 and 61) are disposedlongitudinally between atrial end 24 and ventricular end 26 of frameassembly 22, but not at either of these ends. Further in someembodiments, coupling points 52 are disposed longitudinally betweenatrial end 34 and ventricular end 36 of inner frame tubular portion 32,but not at either of these ends. For example, the coupling points may bemore than 3 mm (e.g., 4-10 mm) both from end 34 and from end 36. It ishypothesized that this advantageously positions the coupling points at apart of inner frame tubular portion 32 that is more rigid than end 34 orend 36.

It is to be noted that ventricular anchor support 50 is expandable intoits radially expanded state (e.g., a released-anchor state) such thatouter frame tissue anchor 54 extends away from axis ax1, independentlyof increasing the diameter of inner frame tubular portion 32 (e.g., asshown in FIGS. 2B & 2D). Similarly, atrial support portion 40 isexpandable into its radially expanded state (e.g., a released-anchorstate) such that it (e.g., inner frame tissue anchors 46 thereof)extends away from axis ax1, independently of increasing the diameter ofinner frame tubular portion 32 (e.g., as shown in FIGS. 2C & 2D). Thestate shown in FIG. 2D may be considered to be an intermediate state.Therefore, prosthetic valve 20 is configured such that ventricularanchor supports 50 (e.g., outer frame tissue anchors 54 thereof) andatrial support portion 40 are expandable such that they both extend awayfrom axis ax1, while retaining a distance d3 therebetween. This distanceis subsequently reducible to a distance d4 by expanding inner frametubular portion 32 (e.g., shown in FIG. 2E).

For some embodiments, while inner frame tubular portion 32 remains inits radially contracted state, outer frame tissue anchor 54 can extendaway from axis ax1 over 40 percent (e.g., 40-80 percent, such as 40-70percent) of the distance that it extends from the axis subsequent to theexpansion of the inner frame tubular portion. For example, forembodiments in which prosthetic valve 20 comprises a outer frame tissueanchor 54 on opposing sides of the prosthetic valve, a span d15 of theouter frame tissue anchors while inner frame tubular portion 32 is inits radially contracted state may be at least 40 percent (e.g., 40-80percent, such as 40-70 percent) as great as a span d16 of the outerframe tissue anchors subsequent to the expansion of the inner frametubular portion. For some embodiments, span d15 is greater than 15 mmand/or less than 50 mm (e.g., 20-30 mm). For some embodiments, span d16is greater than 30 mm and/or less than 60 mm (e.g., 40-50 mm). It is tobe noted that outer frame tissue anchor 54 is effectively fully radiallyexpanded, with respect to other portions of ventricular anchor support50 and/or with respect to inner frame tubular portion 32, before andafter the expansion of the inner frame tubular portion.

Similarly, for some embodiments, while inner frame tubular portion 32remains in its radially contracted state, atrial support portion 40(e.g., inner frame tissue anchors 46) can extend away from axis ax1 over30 percent (e.g., 30-70 percent) of the distance that it extends fromthe axis subsequent to the expansion of the inner frame tubular portion.That is, for some embodiments, a span d17 of the atrial support portionwhile inner frame tubular portion 32 is in its radially contracted statemay be at least 30 percent (e.g., 30-70 percent) as great as a span d18of the atrial support portion subsequent to the expansion of the innerframe tubular portion. For some embodiments, span d17 is greater than 16mm (e.g., greater than 20 mm) and/or less than 50 mm (e.g., 30-40 mm).For some embodiments, span d18 is greater than 40 mm and/or less than 65mm (e.g., 45-56 mm, such as 45-50 mm). It is to be noted that atrialsupport portion 40 is effectively fully radially expanded, with respectto inner frame tubular portion 32, before and after the expansion of theinner frame tubular portion.

It is to be noted that when inner frame tubular portion 32 is radiallyexpanded, outer frame tissue anchors 54 translate radially outward fromspan d15 to span d16 (e.g., without deflecting). In some embodimentsatrial support portion 40 behaves similarly (e.g., inner frame tissueanchors 46 translated radially outward from span d17 to span d18, e.g.,without deflecting). That is, an orientation of each outer frame tissueanchor 54 and/or each inner frame tissue anchor 46 with respect to innerframe tubular portion 32 and/or axis ax1 is the same in the state shownin FIG. 2D as it is in the state shown in FIG. 2E. Similarly, for someembodiments an orientation of each outer frame tissue anchor 54 withrespect to atrial support portion 40 (e.g., with respect to one or moreinner frame tissue anchors 46 thereof) is the same before and afterexpansion of inner frame tubular portion 32.

For some embodiments, increasing the diameter of inner frame tubularportion 32 from d1 to d2 causes greater than 1 mm and/or less than 20 mm(e.g., 1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement ofouter frame tissue anchor 54 away from coupling point 52. For someembodiments, increasing the diameter of inner frame tubular portion 32from d1 to d2 causes greater than 1 mm and/or less than 20 mm (e.g.,1-20 mm, such as 1-10 mm or 5-20 mm) of longitudinal movement of atrialsupport portion 40 toward coupling point 52. For some embodiments,distance d3 is 7-30 mm. For some embodiments, distance d4 is 0-15 mm(e.g., 2-15 mm). For some embodiments, increasing the diameter of innerframe tubular portion 32 from d1 to d2 reduces the distance between theatrial support portion and outer frame tissue anchors 54 by more than 5mm and/or less than 30 mm, such as 5-30 mm (e.g., 10-30 mm, such as10-20 mm or 20-30 mm). For some embodiments, the difference between d3and d4 is generally equal to the difference between d1 and d2. For someembodiments, the difference between d3 and d4 is more than 1.2 and/orless than 3 times (e.g., 1.5-2.5 times, such as about 2 times) greaterthan the difference between d1 and d2.

For some embodiments, outer frame tissue anchors 54 curve such that atip of each outer frame tissue anchor 54 is disposed at a shallowerangle with respect to inner region 42 of atrial support portion 40, thanare portions of ventricular anchor support 50 that are closer toventricular end 26 of frame assembly 22. For some such embodiments, atip of each outer frame tissue anchor may be generally parallel withinner region 42. For some such embodiments, while inner frame tubularportion 32 is in its radially expanded state, a tip portion 55 of eachouter frame tissue anchor 54 that extends from the tip of the outerframe tissue anchor at least 2 mm along the outer frame tissue anchor,is disposed within 2 mm of atrial support portion 40. Thus, for someembodiments, while inner frame tubular portion 32 is in its radiallyexpanded state, for at least 5 percent (e.g., 5-8 percent, or at least 8percent) of span 18 of atrial support portion 40, the atrial supportportion is disposed within 2 mm of an outer frame tissue anchor 54.

For some embodiments, in the absence of any obstruction (such as tissueof the valve or covering 23) between outer frame tissue anchor 54 andatrial support portion 40, increasing the diameter of inner frametubular portion 32 from d1 to d2 causes the outer frame tissue anchor 54and the atrial support portion to move past each other (e.g., the outerframe tissue anchor 54 may move between inner frame tissue anchors 46 ofthe atrial support portion), such that the outer frame tissue anchor 54is closer to the atrial end of prosthetic valve 20 than is the atrialsupport portion, e.g., as shown hereinbelow for frame assemblies 122 and222, mutatis mutandis. (For embodiments in which atrial support portion40 is covered by covering 23, outer frame tissue anchors 54 do not passthe covering. For example, in the absence of any obstruction, outerframe tissue anchors 54 may between inner frame tissue anchors 46, andpress directly against covering 23.) It is hypothesized that for someembodiments this configuration applies greater force to the valve tissuebeing sandwiched, and thereby further facilitates anchoring of theprosthetic valve. That is, for some embodiments, distance d3 is smallerthan the sum of distance d5 and a distance d14 (described with referenceto FIG. 3C). For some embodiments, increasing the diameter of innerframe tubular portion 32 from d1 to d2 advantageously causes outer frametissue anchors 54 and atrial support portion 40 to move greater than 3mm and/or less than 25 mm (e.g., greater than 5 mm and/or less than 15mm, e.g., 5-10 mm, such as about 7 mm) with respect to each other (e.g.,toward each other and then past each other).

In some embodiments, in the radially expanded state of frame assembly22, atrial support portion 40 has an inner region (e.g., an inner ring)42 that extends radially outward at a first angle with respect to axisax1 (and with respect to inner frame tubular portion 32), and an outerregion (e.g., an outer ring) 44 that extends, from the inner region,further radially outward from the inner frame tubular portion at asecond angle with respect to the inner frame tubular portion, the secondangle being smaller than the first angle. For example, for someembodiments inner region 42 extends radially outward at an angle alpha_1of 60-120 degrees (e.g., 70-110 degrees) with respect to axis ax1, andouter region 44 extends radially outward at an angle alpha_2 of 5-70degrees (e.g., 10-60 degrees) with respect to axis ax1.

It is to be noted that angles alpha_1 and alpha_2 are measured betweenthe respective region support portion 40, and the portion of axis ax1that extends in an atrial direction from the level of frame assembly 22at which the respective region begins to extend radially outward.

For some embodiments in which prosthetic valve 20 is configured to beplaced at an atrioventricular valve (e.g., a mitral valve or a tricuspidvalve) of the subject, region 42 is configured to be placed against theatrial surface of the annulus of the atrioventricular valve, and region44 is configured to be placed against the walls of the atrium upstreamof the valve.

For some embodiments, outer region 44 is more flexible than inner region42. For example, and as shown, each inner frame tissue anchor 46 mayhave a different structure in region 44 than in region 42. It ishypothesized that the relative rigidity of region 42 provides resistanceagainst ventricular migration of prosthetic valve 20, while the relativeflexibility of region 44 facilitates conformation of atrial supportportion 40 to the atrial anatomy.

For some embodiments, two or more of inner frame tissue anchors 46 areconnected by a connector (not shown), reducing the flexibility, and/orthe independence of movement of the connected inner frame tissue anchorsrelative to each other. For some embodiments, inner frame tissue anchors46 are connected in particular sectors of atrial support portion 40,thereby making these sectors more rigid than sectors in which the innerframe tissue anchors are not connected. For example, a relatively rigidsector may be provided to be placed against the posterior portion of themitral annulus, and a relatively flexible sector may be provided to beplaced against the anterior side of the mitral annulus, so as to reduceforces applied by atrial support portion 40 on the aortic sinus.

For some embodiments, and as shown, coupling points 52 are disposedcloser to ventricular end 26 of frame assembly 22 than are outer frametissue anchors 54, or is atrial support portion 40.

As described in more detail with respect to FIGS. 4A-F, the movement ofouter frame tissue anchor 54 away from coupling point 52 (and thetypical movement of atrial support portion 40 toward the coupling point)facilitates the sandwiching of tissue of the native valve (e.g., leafletand/or annulus tissue) between the outer frame tissue anchor 54 and theatrial support portion, thereby securing prosthetic valve 20 at thenative valve.

In some embodiments, in the radially contracted state of inner frametubular portion 32, a ventricular end of each ventricular anchor support50 is longitudinally closer than valve-frame coupling elements 31 toventricular end 36, and outer frame tissue anchor 54 of each ventricularanchor support 50 is disposed longitudinally closer than the valve-framecoupling elements to atrial end 34. In some embodiments, this is alsothe case in the radially expanded state of inner frame tubular portion32.

FIGS. 3A-C show structural changes in frame assembly 22 duringtransitioning of the assembly between its radially contracted andradially expanded states, in accordance with some embodiments of theinvention. FIGS. 3A-C each show a portion of the frame assembly, thestructural changes thereof being representative of the structuralchanges that occur in other portions of the frame assembly. FIG. 3Ashows a ventricular anchor support 50 and struts 70 (e.g., a portion ofouter frame 60), and illustrates the structural changes that occuraround outer frame 60. FIG. 3B shows a portion of inner frame 30, andillustrates the structural changes that occur around the inner frame.FIG. 3C shows inner frame 30 as a whole. In each of FIGS. 3A-C, state(A) illustrates the structure while frame assembly 22 (and in particularinner frame tubular portion 32) is in its radially contracted state, andstate (B) illustrates the structure while the frame assembly (and inparticular inner frame tubular portion 32) is in its radially expandedstate.

FIG. 3A shows structural changes in the coupling of ventricularanchoring supports 50 to coupling point 52 (e.g., structural changes ofouter frame 60) during the transitioning of frame assembly 22 (and inparticular inner frame tubular portion 32) between its radiallycontracted and radially expanded states. Each ventricular anchor support50 is coupled to inner frame 30 via at least one strut 70, whichconnects the ventricular anchoring support to coupling point 52. In someembodiments, each ventricular anchor support 50 is coupled to innerframe 30 via a plurality of struts 70. A first end 72 of each strut 70is coupled to ventricular anchor support 50, and a second end 74 of eachstrut is coupled to a coupling point 52. As described hereinabove, forembodiments in which frame 60 comprises ring 66, each ventricular anchorsupport 50 is coupled to the ring at a respective trough 62. Ring 66 maycomprise struts 70, extending between the peaks and troughs, with eachfirst end 72 at (or close to) a trough 62, and each second end 74 at (orclose to) a peak 64. As depicted in FIGS. 1B and 3A, first end 72 mayform the ventricular end 69 of outer frame tubular portion 65.

In the radially contracted state of frame assembly 22 (and in particularof inner frame tubular portion 32), each strut 70 is disposed at a firstangle in which first end 72 is disposed closer than second end 74 to theventricular end of the frame assembly. Expansion of frame assembly 22(and in particular of inner frame tubular portion 32) toward itsradially expanded state causes strut 70 to deflect to a second angle.This deflection moves first end 72 away from the ventricular end offrame assembly 22. That is, in the radially expanded state of frameassembly 22, first end 72 is further from the ventricular end of theframe assembly than it is when the frame assembly is in its radiallycontracted state. This movement is shown as a distance d5 between theposition of end 72 in state (A) and its position in state (B). Thismovement causes the above-described movement of outer frame tissueanchors 54 away from coupling points 52. As shown, outer frame tissueanchors 54 move the same distance d5 in response to expansion of frameassembly 22. Since outer frame tissue anchors 54 and first end 72 (i.e.,ventricular end 69) move the same distance d5 in response to expansionof frame assembly 22, the axial distance (i.e., the distance along axisax1) between outer frame tissue anchors 54 and first end 72 (i.e.,ventricular end 69) may remain constant between the radially expandedstate and the radially contracted state of annular outer frame 60.

For embodiments in which outer frame 60 comprises ring 66, the patternof alternating peaks and troughs may be described as having an amplitudelongitudinally between the peaks and troughs, i.e., measured parallelwith central longitudinal axis ax1 of frame assembly 22, and thetransition between the radially contracted and radially expanded statesmay be described as follows: In the radially contracted state of frameassembly 22 (and in particular of inner frame tubular portion 32), thepattern of ring 66 has an amplitude d20. In the radially expanded stateframe assembly 22 (and in particular of inner frame tubular portion 32),the pattern of ring 66 has an amplitude d21 that is lower than amplituded20. Because (i) it is at peaks 64 that ring 66 is coupled to innerframe 30 at coupling points 52, and (ii) it is at troughs 62 that ring66 is coupled to ventricular anchoring supports 50, this reduction inthe amplitude of the pattern of ring 66 moves ventricular anchoringsupports 50 (e.g., outer frame tissue anchors 54 thereof) longitudinallyfurther from the ventricular end of the frame assembly. The magnitude ofthis longitudinal movement (e.g., the difference between magnitudes d20and d21) is equal to d5.

In some embodiments, distance d5 is the same distance as the distancethat outer frame tissue anchor 54 moves away from coupling point 52during expansion of the frame assembly. That is, a distance betweenouter frame tissue anchor 54 and the portion of ventricular anchorsupport 50 that is coupled to strut 70, remains constant duringexpansion of the frame assembly. For some embodiments, the longitudinalmovement of outer frame tissue anchor 54 away from coupling point 52 isa translational movement (e.g., a movement that does not includerotation or deflection of the outer frame tissue anchor 54).

For some embodiments, a distance d6, measured parallel to axis ax1 offrame assembly 22, between coupling point 52 and first end 72 of strut70 while assembly 22 is in its radially contracted state, is 3-15 mm.For some embodiments, a distance d7, measured parallel to axis ax1,between coupling point 52 and first end 72 of strut 70 while assembly 22is in its radially expanded state, is 1-5 mm (e.g., 1-4 mm).

For some embodiments, amplitude d20 is 2-10 mm (e.g., 4-7 mm). For someembodiments, amplitude d21 is 4-9 mm (e.g., 5-7 mm).

For some embodiments, and as shown, in the radially expanded state,first end 72 of strut 70 is disposed closer to the ventricular end offrame assembly 22 than is coupling point 52. For some embodiments, inthe radially expanded state, first end 72 of strut 70 is disposedfurther from the ventricular end of frame assembly 22 than is couplingpoint 52.

For embodiments in which frame assembly 22 comprises a plurality ofventricular anchoring supports 50 and a plurality of coupling points 52(e.g., for embodiments in which the frame assembly comprises annularouter frame 60) expansion of the frame assembly increases acircumferential distance between adjacent coupling points 52, and anincrease in a circumferential distance between adjacent ventricularanchoring supports 50. FIG. 3A shows such an increase in thecircumferential distance between adjacent coupling points 52, from acircumferential distance d8 in the radially contracted state to acircumferential distance d9 in the radially expanded state. For someembodiments, distance d8 is 1-6 mm. For some embodiments, distance d9 is3-15 mm.

For some embodiments, in addition to being coupled via ring 66 (e.g.,struts 70 thereof) ventricular anchoring supports 50 are also connectedto each other via connectors 78. Connectors 78 allow the describedmovement of ventricular anchoring supports 50 during expansion of frameassembly 22, but stabilize ventricular anchoring supports 50 relative toeach other while the frame assembly is in its radially expanded state.For example, connectors 78 may bend and/or deflect during expansion ofthe frame assembly.

FIGS. 3B-C show structural changes in inner frame 30 during thetransitioning of frame assembly 22 between its radially contracted andradially expanded states. Inner frame tubular portion 32 of inner frame30 is defined by a plurality of cells 80, which are defined by therepeating pattern of the inner frame. When frame assembly 22 is radiallyexpanded from its radially contracted state toward its radially expandedstate, cells 80 (i) widen from a width d10 to a width d11 (measuredorthogonal to axis ax1 of the frame assembly), and (ii) shorten from aheight d12 to a height d13 (measured parallel to axis ax1 of the frameassembly). This shortening reduces the overall height (i.e., alongitudinal length between atrial end 34 and ventricular end 36) ofinner frame tubular portion 32 from a height d22 to a height d23, andthereby causes the above-described longitudinal movement of atrialsupport portion 40 toward coupling points 52 by a distance d14 (shown inFIG. 3C). For some embodiments, and as shown, coupling points 52 aredisposed at the widest part of each cell.

Due to the configurations described herein, the distance by which outerframe tissue anchors 54 move with respect to (e.g., toward, ortoward-and-beyond) atrial support portion 40 (e.g., inner frame tissueanchors 46 thereof), is greater than the reduction in the overall heightof inner frame tubular portion 32 (e.g., more than 20 percent greater,such as more than 30 percent greater, such as more than 40 percentgreater). That is, prosthetic valve 20 comprises: an inner frame (30)that comprises an inner frame tubular portion (32) that circumscribes alongitudinal axis (ax1) of the inner frame so as to define a lumen (38)along the axis, the inner frame tubular portion having an atrial end(34), a ventricular end (36), a longitudinal length therebetween, and adiameter (e.g., d1 or d2) transverse to the longitudinal axis; a valvemember (58), coupled to the inner frame tubular portion, disposed withinthe lumen, and arranged to provide unidirectional atrial-to-ventricularflow of blood through the lumen; an atrial support portion (40), coupledto the inner frame tubular portion; and an annular outer frame (60),coupled to the inner frame tubular portion, and comprising an outerframe tissue anchor (54), wherein: the prosthetic valve has a firststate (e.g., as shown in FIG. 2D and FIG. 4D) and a second state (e.g.,as shown in FIG. 2E and FIG. 4E), in both the first state and the secondstate, (i) the atrial support portion extends radially outward from theinner frame tubular portion, and (ii) the outer frame tissue anchor 54extends radially outward from the inner frame tubular portion, and theinner frame tubular portion, the atrial support portion, and the outerframe are arranged such that transitioning of the prosthetic valve fromthe first state toward the second state: increases the diameter of theinner frame tubular portion by a diameter-increase amount (e.g., thedifference between d1 and d2), decreases the length of the inner frametubular portion by a length-decrease amount (e.g., the differencebetween d22 and d23), and moves the outer frame tissue anchor 54 alongitudinal distance with respect to (e.g., toward ortoward-and-beyond) the atrial support portion (e.g., the differencebetween d3 and d4), this distance being greater than the length-decreaseamount.

As shown in the figures, inner frame 30 is coupled to outer frame 60 bycoupling between (i) a valve-frame coupling element 31 defined by innerframe 30, and (ii) an outer-frame coupling element 61 defined by outerframe 60 (e.g., an outer-frame coupling element is coupled to end 74 ofeach strut). In some embodiments, elements 31 and 61 are fixed withrespect to each other. Each coupling point 52 is thereby defined as thepoint at which a valve-frame coupling element and a correspondingouter-frame coupling element 61 are coupled (e.g., are fixed withrespect to each other). For some embodiments, and as shown, elements 31and 61 are eyelets configured to be coupled together by a connector,such as a pin or suture. For some embodiments, elements 31 and 61 aresoldered or welded together.

In some embodiments, and as shown, valve-frame coupling elements 31 aredefined by inner frame tubular portion 32, and are disposedcircumferentially around central longitudinal axis ax1. Outer-framecoupling elements 61 are coupled to ring 66 (or defined by annular outerframe 60, such as by ring 66) at respective peaks 64.

As shown (e.g., in FIGS. 2A-E), inner frame 30 (e.g., inner frametubular portion 32 thereof) and annular outer frame 60 (e.g., ring 66thereof) are arranged in a close-fitting coaxial arrangement, in boththe radially expanded and radially contracted states of frame assembly22. Ignoring spaces due to the cellular structure of the frames, aradial gap d19 between inner frame 30 (e.g., inner frame tubular portion32 thereof) and outer frame 60 (e.g., ring 66 thereof) may be less than2 mm (e.g., less than 1 mm), in both the radially contracted andradially expanded states, and during the transition therebetween. Thisis facilitated by the coupling between frames 30 and 60, and thebehavior, described hereinabove, of annular outer frame 60 in responseto changes in the diameter of inner frame tubular portion 32 (e.g.,rather than solely due to delivery techniques and/or tools). For someembodiments, more than 50 percent (e.g., more than 60 percent) of ring66 is disposed within 2 mm of inner frame tubular portion 32 in both theradially contracted and radially expanded states, and during thetransition therebetween. For some embodiments, more than 50 percent(e.g., more than 60 percent) of annular outer frame 60, except for outerframe tissue anchors 54, is disposed within 2 mm of inner frame tubularportion 32 in both the radially contracted and radially expanded states,and during the transition therebetween.

The structural changes to frame assembly 22 (e.g., to outer frame 60thereof) are described hereinabove as they occur during (e.g., as aresult of) expansion of the frame assembly (in particular inner frametubular portion 32 thereof). This is the natural way to describe thesechanges because, as described hereinbelow with respect to FIGS. 4A-6,assembly 22 is in its radially contracted state during percutaneousdelivery to the prosthetic valve site, and is subsequently radiallyexpanded. However, the nature of prosthetic valve 20 may be furtherunderstood by describing structural changes that occur duringcompression of the frame assembly (e.g., a transition from the radiallyexpanded state in FIG. 2E to the intermediate state in FIG. 2D), inparticular inner frame tubular portion 32 thereof (including if innerframe tubular portion 32 were radially contracted by application ofcompressive force to the inner frame tubular portion, and not to frame60 except via the inner frame tubular portion pulling frame 60 radiallyinward). Such descriptions may also be relevant because prosthetic valve20 is radially contracted (i.e., “crimped”) soon before its percutaneousdelivery, and therefore these changes may occur while prosthetic valve20 is in the care of the operating physician.

For some embodiments, the fixation of peaks 64 to respective sites ofinner frame tubular portion 32 is such that compression of the innerframe tubular portion from its radially expanded state toward itsradially contracted state such that the respective sites of the innerframe tubular portion pull the peaks radially inward via radially-inwardtension on coupling points 52: (i) reduces a circumferential distancebetween each of the coupling points and its adjacent coupling points(e.g., from d9 to d8), and (ii) increases the amplitude of the patternof ring 66 (e.g., from d21 to d20).

For some embodiments, the fixation of outer-frame coupling elements 61to valve-frame coupling elements 31 is such that compression of innerframe tubular portion 32 from its radially expanded state toward itsradially contracted state such that the valve-frame coupling elementspull the outer-frame coupling elements radially inward: (i) reduces acircumferential distance between each of the outer-frame couplingelements and its adjacent outer-frame coupling elements (e.g., from d9to d8), and (ii) increases the amplitude of the pattern of ring 66(e.g., from d21 to d20).

For some embodiments, the fixation of peaks 64 to the respective sitesof inner frame tubular portion 32 is such that compression of the innerframe tubular portion from its radially expanded state toward itsradially contracted state (i) pulls the peaks radially inward viaradially-inward pulling of the respective sites of the inner frametubular portion on the peaks, (ii) reduces a circumferential distancebetween each of coupling points 52 and its adjacent coupling points(e.g., from d9 to d8), and (iii) increases the amplitude of the patternof ring 66 (e.g., from d21 to d20), without increasing radial gap d19between inner frame 30 (e.g., inner frame tubular portion 32 thereof)and the ring by more than 1.5 mm.

For some embodiments, the fixation of outer-frame coupling elements 61with respect to valve-frame coupling elements 31 is such thatcompression of inner frame tubular portion 32 from its radially expandedstate toward its radially contracted state (i) pulls outer-framecoupling elements 61 radially inward via radially-inward pulling ofvalve-frame coupling elements 31 on outer-frame coupling elements 61,(ii) reduces a circumferential distance between each of the outer-framecoupling elements and its adjacent outer-frame coupling elements (e.g.,from d9 to d8), and (iii) increases the amplitude of the pattern of ring66 (e.g., from d21 to d20), without increasing radial gap d19 betweeninner frame 30 (e.g., inner frame tubular portion 32 thereof) and thering by more than 1.5 mm.

Reference is made to FIGS. 4A-F, which are schematic illustrations ofimplantation of prosthetic valve 20 at a native valve 10 of a heart 4 ofa subject, in accordance with some embodiments of the invention. Valve10 is shown as a mitral valve of the subject, disposed between a leftatrium 6 and a left ventricle 8 of the subject. However prosthetic valve20 may be implanted at another heart valve of the subject, mutatismutandis. Similarly, although FIGS. 4A-F show prosthetic valve 20 beingdelivered transseptally via a sheath 88, the prosthetic valve mayalternatively be delivered by any other suitable route, such astransatrially, or transapically.

Prosthetic valve 20 is delivered, in its radially contracted state, tonative valve 10 using a delivery tool 89 that is operable from outsidethe subject (FIG. 4A). In some embodiments, prosthetic valve 20 isdelivered within a delivery capsule 90 of tool 89, which retains theprosthetic valve in its radially contracted state. A transseptalapproach, such as a transfemoral approach, is shown. In someembodiments, prosthetic valve 20 is positioned such that at least outerframe tissue anchors 54 are disposed in a ventricular direction of thenative valve (i.e., within ventricle 8). At this stage, frame assembly22 of prosthetic valve 20 is as shown in FIG. 2A.

Subsequently, outer frame tissue anchors 54 are allowed to protruderadially outward, as described hereinabove, e.g., by releasing them fromcapsule 90 (FIG. 4B). For example, and as shown, capsule 90 may comprisea distal capsule-portion 92 and a proximal capsule-portion 94, and thedistal capsule-portion may be moved distally with respect to prostheticvalve 20, so as to expose outer frame tissue anchors 54. At this stage,frame assembly 22 of prosthetic valve 20 is as shown in FIG. 2B.

Subsequently, prosthetic valve 20 is moved upstream in an atrialdirection, such that atrial support portion 40, in its radiallycontracted state, is disposed in an atrial direction of leaflets 12(i.e., within atrium 6). For some embodiments, the atrial movement ofprosthetic valve 20 causes outer frame tissue anchors 54 to engageleaflets 12. However, because of the relatively large distance d3provided by prosthetic valve 20 (described hereinabove), for someembodiments it is not necessary to move the prosthetic valve so far inan atrial direction that outer frame tissue anchors 54 tightly engageleaflets 12 and/or pull the leaflets in an atrial direction of the valveannulus. Atrial support portion 40 is then allowed to expand such thatit protrudes radially outward, as described hereinabove, e.g., byreleasing it from capsule 90 (FIG. 4D). For example, and as shown,proximal capsule-portion 94 may be moved proximally with respect toprosthetic valve 20, so as to expose atrial support portion 40. At thisstage, frame assembly 22 of prosthetic valve 20 is as shown in FIG. 2D,in which: (i) distance d3 exists between atrial support portion 40 andouter frame tissue anchors 54, (ii) the outer frame tissue anchors havespan d15, (iii) the atrial support portion has span d17, and (iv) innerframe tubular portion 32 has diameter d1.

In some embodiments, expansion of frame assembly 22 is inhibited bydistal capsule-portion 92 (e.g., by inhibiting expansion of inner frametubular portion 32), and/or by another portion of delivery tool 89(e.g., a portion of the delivery tool that is disposed within lumen 38).

Subsequently, prosthetic valve 20 is allowed to expand toward itsradially expanded state, such that inner frame tubular portion 32 widensto diameter d2, and the distance between atrial support portion 40 andouter frame tissue anchors 54 reduces to distance d4 (FIG. 4E). Thissandwiches tissue of valve 10 (including annular tissue and/or leaflets12 in some embodiments) between atrial support portion 40 and outerframe tissue anchors 54, thereby securing prosthetic valve 20 at thevalve. As depicted in FIG. 4E, atrial support portion 40, includinginner frame tissue anchors 46, may engage atrial tissue of the nativemitral valve (i.e., may engage the native mitral valve from the atrialside) while outer frame tissue anchors may engage ventricular tissue ofthe native mitral valve (i.e., may engage the native mitral valve fromthe ventricular side). FIG. 4F shows delivery capsule 90 having beenremoved from the body of the subject, leaving prosthetic valve 20 inplace at valve 10.

As described hereinabove, prosthetic valve 20 is configured such thatwhen inner frame tubular portion 32 is radially expanded, outer frametissue anchors 54 and atrial support portion 40 move a relatively largedistance toward each other. This enables distance d3 to be relativelylarge, while distance d4 is sufficiently small to provide effectiveanchoring. As also described hereinabove, prosthetic valve 20 isconfigured such that outer frame tissue anchors 54 and atrial supportportion 40 can extend radially outward a relatively large distance whileinner frame tubular portion 32 remains radially contracted. It ishypothesized that for some embodiments, these configurations(independently and/or together) facilitate effective anchoring ofprosthetic valve 20, by facilitating placement of a relatively largeproportion of valve tissue (e.g., leaflets 12) between the outer frametissue anchors 54 and the atrial support portion prior to expandinginner frame tubular portion 32 and sandwiching the valve tissue.

It is further hypothesized that the relatively great radially-outwardextension of outer frame tissue anchors 54 and atrial support portion 40prior to expansion of inner frame tubular portion 32, furtherfacilitates the anchoring/sandwiching step by reducing radially-outwardpushing of the valve tissue (e.g., leaflets 12) during the expansion ofthe inner frame tubular portion, and thereby increasing the amount ofvalve tissue that is sandwiched.

It is yet further hypothesized that this configuration of prostheticvalve 20 facilitates identifying correct positioning of the prostheticvalve (i.e., with atrial support portion 40 in an atrial direction ofleaflets 12 and outer frame tissue anchors 54 in a ventricular directionof the leaflets) prior to expanding inner frame tubular portion 32 andsandwiching the valve tissue.

As shown in FIG. 1A, for some embodiments, in the radially expandedstate of frame assembly 22, prosthetic valve 20 defines a toroidal space49 between outer frame tissue anchors 54 and atrial support portion 40(e.g., a space that is wider than distance d4). For example, space 49may have a generally triangular cross-section. It is hypothesized thatfor some such embodiments, in addition to sandwiching tissue of thenative valve between atrial support portion 40 and outer frame tissueanchors 54 (e.g., the tips of the outer frame tissue anchors), space 49advantageously promotes tissue growth therewithin (e.g., between leaflettissue and covering 23), which over time further secures prostheticvalve 20 within the native valve.

Reference is now made to FIG. 5, which is a schematic illustration of astep in the implantation of prosthetic valve 20, in accordance with someembodiments of the invention. Whereas FIGS. 4A-F show an implantationtechnique in which outer frame tissue anchors 54 are radially expandedprior to atrial support portion 40, for some embodiments the atrialsupport portion is radially expanded prior to the outer frame tissueanchors 54. FIG. 5 shows a step in such an embodiment.

Reference is again made to FIGS. 2A-5. As noted hereinabove, prostheticvalve 20 may be implanted by causing outer frame tissue anchors 54 toradially protrude before causing atrial support portion 40 to radiallyprotrude, or may be implanted by causing the atrial support portion toprotrude before causing the outer frame tissue anchors 54 to protrude.For some embodiments, prosthetic valve 20 is thereby configured to bedeliverable in a ventricular direction (e.g., transseptally, as shown,or transapically) or in an in an atrial direction direction (e.g.,transapically or via the aortic valve). Thus, for some embodiments, anoperating physician may decide which delivery route is preferable for agiven application (e.g., for a given subject, and/or based on availableequipment and/or expertise), and prosthetic valve 20 is responsivelyprepared for the chosen delivery route (e.g., by loading the prostheticvalve into an appropriate delivery tool).

It is to be noted that for some embodiments, ventricular delivery ofprosthetic valve 20 may be performed by expanding outer frame tissueanchors 54 first (e.g., as shown in FIGS. 4A-F) or by expanding atrialsupport portion 40 first (e.g., as shown in FIG. 5). Similarly, for someembodiments atrial delivery of prosthetic valve 20 may be performed byatrial support portion 40 first, or by expanding outer frame tissueanchors 54 first.

Reference is now made to FIG. 6, which is a schematic illustration ofprosthetic valve 20, in the state and position shown in FIG. 4D, inaccordance with some embodiments of the invention. For some embodiments,while prosthetic valve 20 is in the state and position shown in FIG. 4D,leaflets 12 of valve 10 are able to move, at least in part in responseto beating of the heart. Frame (A) shows leaflets 12 during ventricularsystole, and frame (B) shows the leaflets during ventricular diastole.For some such embodiments, blood is thereby able to flow from atrium 6to ventricle 8, between leaflets 12 and prosthetic valve 20. It ishypothesized that this advantageously facilitates a more relaxedimplantation procedure, e.g., facilitating retaining of prosthetic valve20 in this state and position for a duration of greater than 8 minutes.During this time, imaging techniques may be used to verify the positionof prosthetic valve 20, and/or positioning of leaflets 12 between atrialsupport portion 40 and outer frame tissue anchors 54.

Reference is made to FIGS. 7A-B and 8A-B, which are schematicillustrations of frame assemblies 122 and 222 of respective prostheticvalves, in accordance with some embodiments of the invention. Exceptwhere noted otherwise, frame assemblies 122 and 222 may be identical toframe assembly 22, mutatis mutandis. Elements of frame assemblies 122and 222 share the name of corresponding elements of frame assembly 22.Additionally, except where noted otherwise, the prosthetic valves towhich frame assemblies 122 and 222 belong are similar to prostheticvalve 20, mutatis mutandis. FIG. 7A depicts frame assembly 122 in theradially contracted state, while FIG. 7B depicts frame assembly 122 inthe radially expanded state. Similarly, FIG. 8A depicts frame assembly222 in the radially contracted state, while FIG. 8B depicts frameassembly 222 in the radially expanded state. As shown in FIGS. 7A-7B and8A-8B, inner frame tissue anchors 146, 246 and outer frame tissueanchors 154, 254 may be positioned substantially parallel to axis ax1when frame assembly 122, 222 is in the radially contracted state and maydeflect radially outwards away from axis ax1 when frame assembly 122,222 expands into the radially expanded state.

Frame assembly 122 includes an inner frame 130 that includes an innerframe tubular portion 132 having an atrial end 134 and a ventricular end136. One or more projections 128 may extend from ventricular end 136 ofinner frame tubular portion 132. Inner frame tubular portion 132 mayalso include an atrial support portion 140 that may include a pluralityof inner frame tissue anchors 146 extending from inner frame tubularportion 132. Inner frame tissue anchors 146 may connect to inner frametubular portion 132 at connection locations 145, which may be situatedin an intermediate portion of inner frame tubular portion 132 (that is,between atrial end 134 and ventricular end 136). Inner frame tissueanchors 146 may include inner regions 142 and outer regions 144. Asdepicted in FIG. 7B, when frame assembly 122 is in the radially expandedstate, inner regions 142 may extend downwards in a ventriculardirection, while outer regions 144 may extend upwards in an atrialdirection. Frame assembly 122 may also include an outer frame 160 thatcircumscribes the inner frame 130 and which includes an outer frametubular portion 165 having an atrial end 167 and a ventricular end 169.Outer frame 160 may also include a plurality of ventricular anchoringsupports 150 that each include an outer frame tissue anchor 154extending from outer frame tubular portion 165. As depicted in FIG. 7B,outer frame tissue anchors 154 may connect to outer frame tubularportion 165 at connection points 153, and may extend radially outward toterminal ends 155. Connection points 153 may be positioned in anintermediate portion of outer frame tubular portion 165, between atrialend 167 and ventricular end 169. As also depicted in FIG. 7B, when frameassembly 122 is in the radially expanded state, the entire length ofouter frame tissue anchors 154 (i.e., the length extending fromconnection point 153 to terminal end 155) may extend upward towards theatrium of the heart. In some embodiments, outer frame 160 includes aring 166 to which ventricular anchoring supports 150 are coupled. Ring166 is defined by a pattern of alternating peaks and troughs, the peaksbeing fixed to frame 130 at respective coupling points 152, e.g., asdescribed hereinabove for frame assembly 22, mutatis mutandis.

As illustrated in FIG. 7A, when frame assembly 122 is in the radiallycontracted state, the ventricular end 136 of the inner frame tubularportion 132 may be spaced apart from the ventricular end 169 of theouter frame tubular portion 165 relative to axis ax1. In particular,ventricular end 136 of the inner frame tubular portion 132 may bepositioned in a ventricular direction from the ventricular end 169 ofthe outer frame tubular portion. Atrial end 134 of the inner frametubular portion 132 may be positioned in an atrial direction from theatrial end 167 of the outer frame tubular portion 165. However, asillustrated in FIG. 7B, ventricular ends 136, 169 may be configured tobe substantially aligned in a common lateral plane when frame assembly122 is in the radially expanded state. That is, ventricular ends 136,169 may be spaced at substantially the same position along axis ax1 whenframe assembly 122 is in the radially expanded state. As a result,radial expansion of prosthetic valve 120 may decrease the distancebetween ventricular end 136 and ventricular end 169. In addition, and asalso illustrated in FIGS. 7A-7B, inner frame tubular portion 132 mayhave a greater axial length than outer frame tubular portion 165. Forexample, as illustrated in FIG. 7B, ventricular ends 136, 169 of theinner and outer tubular frame portions 132, 165, respectively, may besubstantially aligned, while the atrial end 134 of the inner frametubular portion 132 may extend in an atrial direction beyond the atrialend 167 of the outer frame tubular portion 165.

Frame assembly 222 includes an inner frame 230 that includes an innerframe tubular portion 232 having an atrial end 234 and a ventricular end236. One or more projections 228 may extend from ventricular end 236 ofinner frame tubular portion 232. Inner frame tubular portion 232 mayalso include an atrial support portion 240 that may include a pluralityof inner frame tissue anchors 246 extending from inner frame tubularportion 232. Inner frame tissue anchors 246 may connect to inner frametubular portion 232 at connection locations 245, which may be situatedin an intermediate portion of inner frame tubular portion 232 (i.e.,between atrial end 234 and ventricular end 236). Inner frame tissueanchors 246 may include inner regions 242 and outer regions 244. Asdepicted in FIG. 8B, when frame assembly 222 is in the radially expandedstate, inner regions 242 may extend downwards in a ventriculardirection, while outer regions 244 may extend upwards in an atrialdirection. Frame assembly 222 may also include an outer frame 260 thatcircumscribes the inner frame and which includes an outer frame tubularportion 265 having an atrial end 267 and a ventricular end 269. Outerframe 260 may also include a plurality of ventricular anchoring supports250 that each include an outer frame tissue anchor 254 extending fromouter frame tubular portion 265. As depicted in FIG. 8B, outer frametissue anchors 254 may connect to outer frame tubular portion 265 atconnection points 253, and may extend radially outward to terminal ends255. Connection points 253 may be positioned in an intermediate portionof outer frame tubular portion 265, between atrial end 267 andventricular end 269. As also depicted in FIG. 8B, when frame assembly222 is in the radially expanded state, the entire length of outer frametissue anchors 254 (i.e., the length extending from connection points253 to terminal ends 255) may extend upward towards an atrium. In someembodiments, outer frame 260 includes a ring 266 to which ventricularanchoring supports 250 are coupled. Ring 266 is defined by a pattern ofalternating peaks and troughs, the peaks being fixed to frame 230 atrespective coupling points 252, e.g., as described hereinabove for frameassembly 22, mutatis mutandis.

As illustrated in FIG. 8A, when frame assembly 222 is in the radiallycontracted state, the ventricular end 236 of the inner frame tubularportion may be spaced apart from the ventricular end 269 of the outerframe tubular portion relative to axis ax1. In particular, ventricularend 236 may be positioned in a ventricular direction from ventricularend 269 when frame assembly 222 is in the radially contracted state. Inaddition, as illustrated in FIG. 8B, ventricular ends 236, 269 of theinner and outer frame tubular portions 232, 265, respectively, may beconfigured to be substantially aligned in a common lateral plane whenframe assembly 222 is in the radially expanded state. That is,ventricular ends 236, 269 may be spaced at substantially the sameposition along axis ax1 when frame assembly 222 is in the radiallyexpanded state.

Whereas inner frame tissue anchors 46 of frame assembly 22 are shown asextending from atrial end 34 of inner frame tubular portion 32, innerframe tissue anchors 146 and 246 of frame assemblies 122 and 222,respectively, may extend from sites further in a ventricular direction.(This difference may also be made to frame assembly 22, mutatismutandis.) Inner frame tubular portions 32, 132 and 232 are each definedby a repeating pattern of cells that extends around the centrallongitudinal axis. In some embodiments, and as shown, inner frametubular portions 32, 132 and 232 are each defined by two stacked,tessellating rows of cells. In the radially expanded state of each innerframe tubular portion, these cells may be narrower at their atrial andventricular extremities than midway between these extremities. Forexample, and as shown, the cells may be roughly diamond or astroid inshape. In frame assembly 22, each inner frame tissue anchor 46 isattached to and extends from a site 35 that is at the atrial extremityof cells of the atrial row. In contrast, in frame assemblies 122 and222, each inner frame tissue anchor 146 or 246 is attached to andextends from a site 135 (assembly 122) or 235 (assembly 222) that is atthe connection between two adjacent cells of the atrial row(alternatively described as being at the atrial extremity of cells ofthe ventricular row).

It is hypothesized by the inventors that this lower position of theinner frame tissue anchors, while maintaining the length of the lumen ofthe inner frame tubular portion, advantageously reduces the distancethat the inner frame tubular portion (i.e., the ventricular end thereof)extends into the ventricle of the subject, and thereby reduces alikelihood of inhibiting blood flow out of the ventricle through theleft ventricular outflow tract. It is further hypothesized that thisposition of the inner frame tissue anchors reduces radial compression ofthe inner frame tubular portion by movement of the heart, due to greaterrigidity of the inner frame tubular portion at sites 135 and 235 (whichis supported by two adjacent cells) than at site 35 (which is supportedby only one cell).

As illustrated in FIG. 7B, when frame assembly 122 is in the radiallyexpanded state, connection locations 145 of the inner frame tissueanchors 146 may be positioned in an atrial direction from the atrial end167 of the outer frame tubular portion 165. As a result, outer frametubular portion 165 may be positioned in a ventricular direction fromconnection locations 145 and from inner frame tissue anchors 146.

As depicted in FIGS. 7B and 8B, and as discussed above, ventricular end169, 269 of the outer frame tubular portion 165, 265 may besubstantially aligned with the ventricular end 136, 236 of the innerframe tubular portion 132, 232 when frame assembly 122, 222 is expanded.Meantime, atrial end 134, 234 of the inner frame tubular portion may132, 232 extend in an atrial direction beyond the atrial end 167, 267 ofthe outer frame tubular 165, 265 when frame assembly 122, 222 isexpanded. Thus, in at least some embodiments, a distance betweenventricular end 169, 269 of the outer frame tubular portion 165, 265 andventricular end 136, 236 of the inner frame tubular portion 132, 232 maybe smaller than a distance between atrial end 167, 267 of the outerframe tubular portion 165, 265 and atrial end 134, 234 of the innerframe tubular portion 132, 232.

As shown, in the radially expanded state of frame assemblies 22, 122,and 222, the ventricular anchoring supports (50, 150, and 250,respectively) (and thus outer frame tissue anchors 54, 154, 254) arecircumferentially staggered with the inner frame tissue anchors (46,146, and 246, respectively). This may allow the ventricular anchoringsupports 50 to move in an atrial direction between the inner frametissue anchors during expansion of the inner frame tubular portion (32,132 and 232, respectively), facilitating application of greatersandwiching force on tissue of the native valve. The lower position ofthe inner frame tissue anchors of assemblies 122 and 222 includescircumferentially shifting the position of the inner frame tissueanchors by the width of half a cell. In order to maintain thecircumferential staggering of the inner frame tissue anchors 46, 146,246 and outer frame tissue anchors 54, 154, 254, rings 166 and 266 (andthereby ventricular anchoring supports 150 and 250) arecircumferentially shifted correspondingly. As a result, whereas thepeaks of ring 66 generally align with connections between adjacent cellsof the ventricular row of cells of inner frame tubular portion 32 (andare fixed to these sites), the peaks of rings 166 and 266 are generallyaligned midway between these sites (i.e., at spaces of the cellularstructure of the inner frame tubular portion). An appendages 168 (forassembly 122) or 268 (for assembly 222) facilitate fixing of the peakwith respect to the tubular structure.

For assembly 122, appendages 168 are defined by inner frame 130 (e.g.,by inner frame tubular portion 132 thereof) and extend (in a ventriculardirection) to the peaks of ring 166, to which they are fixed. Forexample, each appendage 168 may define a valve-frame coupling element131 that is fixed to a respective outer-frame coupling element 161defined by outer frame 260. In some embodiments, appendages 168 extendfrom sites 135. In some embodiments, appendages 168 are integral withinner frame tubular portion 132 and/or in-plane with the inner frametubular portion (e.g., are part of its tubular shape). As illustrated inFIG. 7B, coupling element 161 may be spaced apart from the atrial 167and ventricular 169 ends of the outer frame tubular portion 165, whilecoupling element 131 may be spaced apart from the atrial 134 andventricular 136 ends of the inner frame tubular portion 132. As aresult, and as also illustrated in FIG. 7B, outer frame tubular portion165 may have no connections to inner frame tubular portion 132 alongventricular end 169 of the outer frame tubular portion 165.Additionally, inner frame tubular portion 132 may have no connections toouter frame tubular portion 165 along ventricular end 136 of the innerframe tubular portion 132.

For assembly 222, appendages 268 are defined by outer frame 260, andextend (e.g., in an atrial direction) from the peaks of ring 266. Insome embodiments, appendages 268 extend to sites 235, to which they arefixed. For example, each appendage 268 may define an outer framecoupling element 261 that is fixed to a respective inner frame couplingelement 231 defined by inner frame 230 (e.g., by inner frame tubularportion 232 thereof). In some embodiments, appendages 268 are integralwith outer frame 260 and/or in-plane with adjacent portions of outerframe 260, such as ring 266.

Therefore, frame assembly 122 defines a hub at site 135, and frameassembly 222 defines a hub at site 235. For some embodiments, apparatustherefore comprises: a plurality of prosthetic valve leaflets; and aframe assembly, comprising: an inner frame tubular portion (132 or 232)defined by a repeating pattern of cells, the inner frame tubular portionextending circumferentially around longitudinal axis ax1 so as to definea longitudinal lumen, the prosthetic valve leaflets coupled to the innerframe and disposed within the lumen; an outer frame (160 or 260),comprising a plurality of ventricular anchoring supports (150 or 250),distributed circumferentially around the inner frame tubular portion,each support having an outer frame tissue anchor (154 or 254); an atrialsupport portion (140 or 240) that comprises a plurality of inner frametissue anchors (146 or 246) that extend radially outward from the innerframe tubular portion; and a plurality of appendages (168 or 268), eachhaving a first end that defines a coupling element (161 or 261) viawhich the inner frame tubular portion is coupled to the outer frame, anda second end; wherein the frame assembly defines a plurality of hubs(135 or 235), distributed circumferentially around the longitudinal axison a plane that is transverse to longitudinal axis ax1, each hub definedby convergence and connection of, (i) two adjacent cells of the innerframe tubular portion, (ii) an inner frame tissue anchor of theplurality of inner frame tissue anchors, and (iii) an appendage of theplurality of appendages.

Reference is made to FIGS. 9A-C, which are schematic illustrations of anprosthetic valve 320 comprising a frame assembly 322, in accordance withsome embodiments of the invention. Except where noted otherwise, frameassembly 322 is identical to frame assembly 122, and prosthetic valve300 is identical to the prosthetic valve to which frame assembly 122belongs, mutatis mutandis. FIG. 9A is a side-view of prosthetic valve320, and FIG. 9B is an isometric bottom-view of the prosthetic valve.

Frame assembly 122 comprises (i) an inner frame 330 that comprises aninner frame tubular portion 332 and an atrial support portion 340 thatcomprises a plurality of inner frame tissue anchors 346, and (ii) anouter frame 360 that circumscribes the inner frame, and comprises aplurality of ventricular anchoring supports 350 that each comprise anouter frame tissue anchor 354. In some embodiments, outer frame 360comprises a ring 366 to which ventricular anchoring supports 350 arecoupled. Ring 366 is defined by a pattern of alternating peaks andtroughs, the peaks being fixed to frame 330 at respective couplingpoints 352, e.g., as described hereinabove for frame assembly 22 and/orframe assembly 122, mutatis mutandis.

Frame assembly 322 comprises an annular atrial support portion 340 thathas an inner portion 342 that extends radially outward from the atrialportion (e.g., the atrial end) of inner frame tubular portion 332.Atrial support portion 340 further comprises one or more fabric pockets344 disposed circumferentially around inner portion 342, each pocket ofthe one or more pockets having an opening that faces a ventriculardirection (i.e., generally toward the ventricular end of prostheticvalve 320). In the figures, atrial support portion 340 has a singletoroidal pocket 344 that extends circumferentially around inner portion342.

In some embodiments, a covering 323 (e.g., similar to covering 23,described hereinabove, mutatis mutandis) is disposed over inner frametissue anchors 346, thereby forming pocket 344. Further in someembodiments, inner frame tissue anchors 346 are shaped to form pocket344 from covering 323. For example, and as shown, inner frame tissueanchors 346 may curve to form a hook-shape.

For some embodiments, portion 340 has a plurality of separate pockets344, e.g., separated at inner frame tissue anchors 346. For some suchembodiments, covering 323 is loosely-fitted (e.g., baggy) betweenradially-outward parts of inner frame tissue anchors 346, e.g., comparedto inner portion 342, in which the covering is more closely-fittedbetween radially-inward parts of the inner frame tissue anchors.

FIG. 9C shows prosthetic valve 320 implanted at native valve 10. Pocket344 is shaped and arranged to billow in response to perivalvular flow302 of blood in an atrial direction. If ventricular systole forces bloodin ventricle 8 between prosthetic valve 320 and native valve 10, thatblood inflates pocket 344 and presses it (e.g., covering 323 and/or theradially-outward part of inner frame tissue anchor 346) against tissueof atrium 6 (e.g., against the atrial wall), thereby increasing sealingresponsively. It is hypothesized by the inventors that the shape andorientation of pocket 344 (e.g., the hook-shape of inner frame tissueanchors 346) facilitates this pressing radially-outward in response tothe pocket's receipt of blood flowing in an atrial direction (that is,towards the atrium).

Pocket(s) 344 may be used in combination with any of the prostheticvalves described herein, mutatis mutandis.

Reference is again made to FIGS. 1A-9C. It is to be noted that unlessspecifically stated otherwise, the term “radially outward” (e.g., usedto describe atrial support portion 40 and outer frame tissue anchors 54)means portions of the element are disposed progressively further outwardfrom a central point (such as longitudinal axis ax1 or inner frametubular portion 32), but does not necessarily mean disposed at 90degrees with respect to longitudinal axis ax1. For example, outer frametissue anchors 54 may extend radially outward at 90 degrees with respectto longitudinal axis ax1, but may alternatively extend radially outwardat a shallower angle with respect to the longitudinal axis.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1-72. (canceled)
 73. An expandable prosthetic valve for implantationwithin a native mitral valve, the prosthetic valve being expandable froma radially contracted state to a radially expanded state, the prostheticvalve comprising: an expandable annular outer frame having a ventricularend; and an expandable inner frame situated at least partially withinthe annular outer frame and having a ventricular end, the inner framefurther including one or more tissue anchors extending therefrom,wherein the annular outer frame and the inner frame are configured andinterconnected in a manner such that the ventricular end of the annularouter frame and the ventricular end of the inner frame are substantiallyaligned in a common plane when the annular outer frame and the innerframe are both in the radially expanded state, and the ventricular endof the annular outer frame and the ventricular end of the inner frameare not substantially aligned in the common plane when the annular outerframe and the inner frame are both in the radially contracted state. 74.The prosthetic valve of claim 73, wherein the common plane is a lateralplane.
 75. The prosthetic valve of claim 73, further comprising one ormore tissue anchors extending from the annular outer frame.
 76. Theprosthetic valve of claim 75, wherein the one or more tissue anchors areconfigured to engage ventricular tissue of the native mitral valve, andwherein the one or more tissue anchors extending from the inner frameare configured to engage atrial tissue of the native mitral valve. 77.The prosthetic valve of claim 75, wherein a connection between the innerframe and the annular outer frame is located at a portion of theprosthetic valve spaced apart from the atrial and ventricular ends ofthe inner frame and from the atrial and ventricular ends of the annularouter frame.
 78. The prosthetic valve of claim 75, configured such thatupon implantation, an entire length of at least one tissue anchorextends from the annular outer frame toward an atrium, and a portion ofat least one tissue anchor extends from the inner frame extends toward aventricle.
 79. The prosthetic valve of claim 75, wherein the annularouter frame further includes an atrial end opposite the ventricular end,and an intermediate portion extending between the atrial end of theannular outer frame and the ventricular end of the annular outer frame;and wherein at least one tissue anchor extends from the intermediateportion of the annular outer frame.
 80. The prosthetic valve of claim75, wherein an axial distance between the tissue anchors extending fromthe annular outer frame and the ventricular end of the annular outerframe remains constant between the radially expanded state of theannular outer frame and the radially contracted state of the annularouter frame.
 81. The prosthetic valve of claim 73, wherein the innerframe further includes an atrial end opposite the ventricular end, andan intermediate portion extending between the atrial end of the innerframe and the ventricular end of the inner frame; and wherein at leastone tissue anchor extends from the intermediate portion of the innerframe.
 82. The prosthetic valve of claim 73, wherein the annular outerframe has no connections to the inner frame along the ventricular end ofthe annular outer frame, and wherein the inner frame has no connectionsto the annular outer frame along the ventricular end of the inner frame.83. The prosthetic valve of claim 73, wherein the inner frame has agreater axial length than an axial length of the annular outer frame.84. The prosthetic valve of claim 73, wherein when the annular outerframe and the inner frame are both in the radially contracted state, theinner frame extends beyond the ventricular end of the annular outerframe in a ventricular direction and beyond an atrial end of the annularouter frame in an atrial direction.
 85. The prosthetic valve of claim73, configured such that radial expansion of the annular outer frame andof the inner frame decreases a distance between the ventricular end ofthe annular outer frame and the ventricular end of the inner frame. 86.The prosthetic valve of claim 73, wherein when the annular outer frameand the inner frame are both in the radially contracted state, at leastone tissue anchor is configured for radially outward deployment.
 87. Theprosthetic valve of claim 73, wherein when the annular outer frame andthe inner frame are both in the radially contracted state, at least onetissue anchor extends in a direction substantially parallel to alongitudinal axis of the prosthetic valve.
 88. The prosthetic valve ofclaim 73, wherein when the annular outer frame and the inner frame areboth in the radially expanded state, at least a majority of the annularouter frame is positioned in a ventricular direction from the at leastone tissue anchor.
 89. The prosthetic valve of claim 73, wherein adistance between the ventricular end of the annular outer frame and theventricular end of the inner frame is smaller than a distance between anatrial end of the annular outer frame and an atrial end of the innerframe.
 90. A prosthetic valve for implantation within a native heartvalve, the prosthetic valve configured to expand from a radiallycontracted state to a radially expanded state, the prosthetic valvecomprising: an annular outer frame having an atrial end and aventricular end; and an inner frame situated at least partially withinthe annular outer frame and having a ventricular end, wherein a locationof connection between the annular outer frame and the inner frame isspaced apart from the atrial end of the annular outer frame and from theventricular end of the annular outer frame, and wherein the annularouter frame and the inner frame are configured and interconnected in amanner such that radial expansion of the annular outer frame and of theinner frame decreases a distance between the ventricular end of theannular outer frame and the ventricular end of the inner frame.
 91. Theprosthetic valve of claim 90, wherein the annular outer frame and theinner frame are configured such that: the ventricular end of the annularouter frame and the ventricular end of the inner frame are substantiallyaligned in a common plane when the annular outer frame and the innerframe are both in the radially expanded state, and the ventricular endof the annular outer frame and the ventricular end of the inner frameare not substantially aligned in the common plane when the annular outerframe and the inner frame are both in the radially contracted state. 92.The prosthetic valve of claim 90, further comprising a plurality oftissue anchors extending from the inner frame, wherein at least onetissue anchor extends from a portion of the inner frame spaced from anatrial end of the inner frame and from the ventricular end of the innerframe.